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Fulltext Utility of Ki-67 and p53 in distinguishing cervical intraepithelial neoplasia 3 from squamous cell carcinoma of the cervix

Tan GC, Sharifah NA, Shiran MS, Salwati S, Hatta AZ, Paul-Ng HO

Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):781-4.
PMID: 19256776

The differentiation between cervical intraepithelial neoplasia 3 (CIN 3) and early squamous cell carcinoma (SCC) of the cervix may be difficult in certain situations. Identification of invasion beyond the basement membrane is the gold standard for the diagnosis of the latter. The objective of this study was to determine whether the use of Ki-67 and p53 could help in solving the above dilemma. This was a retrospective study on 61 cases of cervical neoplasms comprising of 25 cases of CIN 3 and 36 SCC. All cases were evaluated by immunohistochemistry using Ki-67 and p53 monoclonal antibodies. Results showed that the differences of Ki-67 and p53 expression between CIN 3 and SCC were statistically significant. In conclusion, Ki-67 and p53 may serve as helpful adjuncts to routinely-stained histological sections in differentiating between CIN 3 and SCC.

Matched MeSH terms: Ki-67 Antigen/analysis*
The role of CD30, CD40 and CD95 in the regulation of proliferation and apoptosis in classical Hodgkin's lymphoma

Kim LH, Eow GI, Peh SC, Poppema S

Pathology, 2003 Oct;35(5):428-35.
PMID: 14555388

AIMS: CD30, CD40 and CD95 are members of the tumour necrosis factor receptor superfamily. Ligation to their respective ligands (CD30L, CD40L, CD95L) will generate a diverse set of signalling cascades. We aim to study the expression pattern of CD30, CD40 and CD95 in classical Hodgkin's lymphoma (cHL) and to correlate the expressions with proliferation and apoptosis in the Hodgkin/Reed-Sternberg (H/RS) cells of cHL with or without associated Epstein-Barr virus (EBV) infection.
METHODS: A total of 66 cHL cases were retrieved from the archives. Expressions of CD30, CD40, CD95 and proliferation by Ki-67 expression were detected with an immunohistochemical staining method. Apoptosis index was assessed by in situ TUNEL staining technique on 30 randomly selected cases and the presence of EBV was determined by EBER in situ hybridisation.
RESULTS: Expression of CD30, CD40 and CD95 in the H/RS cells was observed in a high proportion of the cases (100, 93.9, 90.5%, respectively). There was no significant association or correlation of the expression of these molecules with the presence of EBV. Expression of CD40 was associated with expression of the proliferation marker Ki-67 (P=0.044), whereas strong (intermediate and high) expression of CD30 showed a significant correlation with proliferation in the EBV-negative cases only (P=0.025). No correlation was observed for the expression of CD30 and CD40 with apoptosis of the H/RS cells. The childhood cases showed weaker CD95 expression in the H/RS cells than the adult cases, and the expression of CD95 was weaker than that of CD40 in the childhood group.
CONCLUSIONS: Our results showed that CD30, CD40 and CD95 are highly expressed in the H/RS cells of the majority of cases of cHL. The expression patterns seem to be independent of EBV and do not correlate with apoptosis of the H/RS cells.

Matched MeSH terms: Ki-67 Antigen/metabolism
The pattern of Ki-67 and bcl-2 expression in lymphoid malignancies

Wang PL, Peh SC

Malays J Pathol, 1997 Jun;19(1):59-64.
PMID: 10879243

The International Working Formulation divides non-Hodgkin's lymphoma (NHL) into three grades: low, intermediate and high. This grading system implies rate of tumour growth and hence prognosis. Ki-67 antigen is a proliferation-related nuclear antigen and bcl-2 oncogene product is known to inhibit apoptosis. This study aimed to determine the pattern of expression of Ki-67 antigen and bcl-2 oncoprotein in various grades of NHL. Paraffin-embedded tissues from 42 cases of NHL (7 low, 15 intermediate, 20 high grade) were retrieved from the files of the Department of Pathology, University of Malaya. Ki-67 antigen and bcl-2 oncoprotein were detected using immunohistochemistry. The percentage of positively stained neoplastic cells was determined by semi-quantitative estimation and given scores ranging from 0 to 6. Partition chi square test demonstrated the association of Ki-67 antigen expression and histological grade (p = 0.007). There was no significant difference in Ki-67 antigen expression between intermediate and high grade malignant lymphomas (p = 0.28), whereas significant difference was demonstrated between low and intermediate/high grade tumours (p = 0.003). Bcl-2 oncoprotein expression in the neoplastic cells varied widely within the three histological grades. Statistical analysis showed no association between the expression of bcl-2 oncoprotein and histological grade (p = 0.25). Ki-67 immunostaining is therefore a useful adjunct to histological grading of NHL.

Matched MeSH terms: Ki-67 Antigen/metabolism*
The expression of Bcl-2 by proliferating cells varies in different categories of B-cell lymphoma

Masir N, Jones M, Lee AM, Goff LK, Clear AJ, Lister A, et al.

Histopathology, 2010 Apr;56(5):617-26.
PMID: 20459572 DOI: 10.1111/j.1365-2559.2010.03524.x

To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.

Matched MeSH terms: Ki-67 Antigen/metabolism
Fulltext The anti-cancer property of proteins extracted from Gynura procumbens (Lour.) Merr

Hew CS, Khoo BY, Gam LH

PLoS One, 2013;8(7):e68524.
PMID: 23874655 DOI: 10.1371/journal.pone.0068524

Gynura procumbens (Lour.) Merr. belongs to the Asteraceae Family. The plant is a well-known traditional herb in South East Asia and it is widely used to treat inflammation, kidney discomfort, high cholesterol level, diabetic, cancer and high blood pressure. Our earlier study showed the presence of valuable plant defense proteins, such as peroxidase, thaumatin-like proteins and miraculin in the leaf of G. procumbens. However, the effects of these defense proteins on cancers have never been determined previously. In the present study, we investigated the bioactivity of gel filtration fractionated proteins of G. procumbens leaf extract. The active protein fraction, SN-F11/12, was found to inhibit the growth of a breast cancer cell line, MDA-MB-231, at an EC50 value of 3.8 µg/mL. The mRNA expressions of proliferation markers, Ki67 and PCNA, were reduced significantly in the MDA-MB-23 cells treated with SN-F11/12. The expression of invasion marker, CCL2, was also found reduced in the treated MDA-MB-231 cells. All these findings highlight the anti-cancer property of SN-F11/12, therefore, the proteins in this fraction can be a potential chemotherapeutic agent for breast cancer treatment.

Matched MeSH terms: Ki-67 Antigen/metabolism
Roles of Ki67 in Breast Cancer - Important for Management?

Yip Ch, Bhoo-Pathy N, Daniel J, Foo Y, Mohamed A, Abdullah M, et al.

Asian Pac J Cancer Prev, 2016;17(3):1077-82.
PMID: 27039727

BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer.
MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22.
RESULTS: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy.
CONCLUSIONS: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

Matched MeSH terms: Ki-67 Antigen/metabolism*
Fulltext Role of co-expression of estrogen receptor beta and Ki67 in prostate adenocarcinoma

Azizan N, Hayati F, Tizen NMS, Farouk WI, Masir N

Investig Clin Urol, 2018 07;59(4):232-237.
PMID: 29984337 DOI: 10.4111/icu.2018.59.4.232

Purpose: To evaluate the expression of estrogen receptor (ER)-beta and Ki67 in prostate cancer and study their relationship.
Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.
Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.
Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.

Matched MeSH terms: Ki-67 Antigen/metabolism*
Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction

Naidu R, Wahab NA, Yadav M, Kutty MK

Int J Mol Med, 2002 Feb;9(2):189-96.
PMID: 11786932

Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.

Matched MeSH terms: Ki-67 Antigen/analysis
Protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats

Koriem KM, Fathi GE, Salem HA, Akram NH, Gamil SA

Toxicol. Mech. Methods, 2013 May;23(4):263-72.
PMID: 23193971 DOI: 10.3109/15376516.2012.748857

Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.

Matched MeSH terms: Ki-67 Antigen/metabolism
Fulltext Neuroendocrine tumour of the lung: a diagnostic challenge

Nur Hidayah Bahrom, Anis Safura Ramli, Nor Suraya Samsudin, Norliana Dalila Mohamad Ali, Nor Salmah Bakar

Journal of Clinical and Health Sciences, 2019;4(2):97-104.
MyJurnal

This is a case of a 62-year-old Indian man who was diagnosed with a rare type of lung
neuroendocrine tumour (NET) of atypical carcinoid (AC) subtype which comprises only 0.1%–
0.2% of pulmonary neoplasms. He initially presented to a private hospital in May 2018 with a
6-month history of chronic productive cough and haemoptysis. Chest X-Ray (CXR), CT scan,
bronchoscopy, biopsy and broncho-alveolar lavage were conducted. At this stage, imaging and
histopathological investigations were negative for malignancy. Diagnosis of bronchiectasis was
made and he was treated with antibiotic and tranexamic acid. Due to financial difficulties, his
care was transferred to a university respiratory clinic in June 2018. His condition was monitored
with CXR at every visit and treatment with tranexamic acid was continued for 6 months.
However, due to persistent haemoptysis, he presented to the university primary care clinic in
Dec 2018. Investigations were repeated in January 2019 where his CXR showed increased
opacity of the left retrocardiac region and CT scan revealed a left lower lobe endobronchial
mass causing collapse with mediastinal lymphadenopathy suggestive of malignancy.
Bronchoscopy, biopsy and histopathology confirmed the presence of NET. Although the Ki-67
index was low, the mitotic count, presence of necrosis and evidence of liver metastases
favoured the diagnosis of AC. A positron emission tomography Ga-68 DONATOC scan showed
evidence of somatostatin receptor avid known primary malignancy in the lungs with suspicions
of liver metastasis. He was subsequently referred to the oncology team and chemotherapy was
initiated. This case highlights the challenge in diagnosis and management of patients with AC.
Physicians ought to be vigilant and have a high index of suspicion in patients who present with
persistent symptoms on multiple visits. Early diagnosis of NET would prevent metastasis and
provide better prognosis. Continuous follow-up shared care between primary care and
secondary care physicians is also essential to provide ongoing psychosocial support for
patients with NET, especially those with metastatic disease

Matched MeSH terms: Ki-67 Antigen
Fulltext Modulation of Ki67 and myogenic regulatory factor expression by tocotrienol-rich fraction ameliorates myogenic program of senescent human myoblasts

Tan CM, Najib NAM, Suhaimi NF, Halid NA, Cho VV, Abdullah SI, et al.

Arch Med Sci, 2021;17(3):752-763.
PMID: 34025846 DOI: 10.5114/aoms.2019.85449

Introduction: Replicative senescence results in dysregulation of cell proliferation and differentiation, which plays a role in the regenerative defects observed during age-related muscle atrophy. Vitamin E is a well-known antioxidant, which potentially ameliorates a wide range of age-related manifestations. The aim of this study was to determine the effects of tocotrienol-rich fraction (TRF) in modulating the expression of proliferation- and differentiation-associated proteins in senescent human myoblasts during the differentiation phase.
Material and methods: Human skeletal muscle myoblasts were cultured until senescence. Young and senescent cells were treated with TRF for 24 h before and after differentiation induction, followed by evaluation of cellular morphology and efficiency of differentiation. Expression of cell proliferation marker Ki67 protein and myogenic regulatory factors MyoD and myogenin were determined.
Results: Our findings showed that treatment with TRF significantly improved the morphology of senescent myoblasts. Promotion of differentiation was observed in young and senescent myoblasts with TRF treatment as shown by the increased fusion index and larger size of myotubes. Increased Ki67 and myogenin expression with TRF treatment was also observed in senescent myoblasts, suggesting amelioration of the myogenic program by TRF during replicative senescence.
Conclusions: TRF modulates the expression of regulatory factors related to proliferation and differentiation in senescent human myoblasts and could be beneficial for ameliorating the regenerative defects during aging.

Matched MeSH terms: Ki-67 Antigen
Mechanisms of the In Vivo Antitumor Activity of Polyalthia longifolia Leaf Extract Against HeLa Cell Xenograft Tumor: A Microscopic-Based Histological and Immunohistochemical Microanalyses

Cilwyn-Shalitha B, Sasidharan S

Microsc Microanal, 2023 Jun 09;29(3):1153-1167.
PMID: 37749670 DOI: 10.1093/micmic/ozad023

The present study investigated the effects of Polyalthia longifolia leaf extract against the growth of HeLa cell xenograft tumor in nude mice and its underlying mechanism. The nude mice xenografted with HeLa cells were treated with 5% DMSO (vehicle control), 20 mg/kg/body weight of etoposide (positive control), and 500 and 1000 mg/kg/body weight of leaf extract, respectively. Antitumor activity was evaluated with apoptosis, proliferation, and angiogenesis using microscopic-based histological and immunohistochemical microanalyses. The tumor tissue histological and immunohistochemical analyses showed that the HeLa tumor cell death was associated with apoptosis and decreased (p < 0.05) expression of Ki-67 in tumor tissues. The extract also inhibits tumor angiogenesis by downregulating (p < 0.05) the expression of VEGF and CD31 in tumor tissues after treatment for 35 days. Conclusively, the P. longifolia leaf extract effectively inhibited HeLa cell xenograft growth in nude mice. The possible mechanism was related to induction of apoptosis, inhibition of tumor HeLa cell proliferation by decreasing the Ki-67 protein expression, and prevention of tumor angiogenesis by reducing VEGF and CD31 protein expression in HeLa cells.

Matched MeSH terms: Ki-67 Antigen
Fulltext Ki67 and P53 Expression in Relation to Clinicopathological Features in Phyllodes Tumour of the Breast

Mohd Ali NA, Nasaruddin AF, Mohamed SS, Wan Rahman WF

Asian Pac J Cancer Prev, 2020 Sep 01;21(9):2653-2659.
PMID: 32986365 DOI: 10.31557/APJCP.2020.21.9.2653

OBJECTIVE: Phyllodes tumour (PT) is a rare fibroepithelial neoplasm of the breast that carries a risk of malignancy. Histopathological examination remains a gold standard for diagnosis. The usage of the immunohistochemical markers of Ki67 and p53 acts as a supplement method, particularly for the malignant PT. We aim here to study the expression of these markers in PT and to see their relation to the tumour grading.
METHODOLOGY: We conducted a retrospective cross-sectional study on 57 archived formalin-fixed paraffin-embedded tissue blocks of PT from the years 2015 to 2018 from two hospitals in East Coast Malaysia. The histopathological examination and immunohistochemical stain for Ki67 and p53 were analysed.
RESULTS: There was an association between clinical descriptive data of skin changes, lump size of more than 3 cm, cytological atypia, stromal hypercellularity, mitosis and immunohistochemistry with the clinical diagnosis of PT. Both marked expression of Ki67 and p53 were seen in borderline and malignant PT. Our study showed that in the presence of high mitotic figures, marked expression of Ki67 was only seen in cases of malignant PT.
CONCLUSION: We found a significant association of Ki67 and p53 expressions, high mitosis and other descriptive histopathological features in malignant PT. Further study with larger sample size is recommended to predict tumour grade and prognosis as well as the disease-free survival of the tumour.
.

Matched MeSH terms: Ki-67 Antigen/metabolism*
Fulltext Ki-67 immuno-histochemistry index in stage III giant cell tumor of the bone

Ismail FW, Shamsudin AM, Wan Z, Daud SM, Samarendra MS

J Exp Clin Cancer Res, 2010 Mar 12;29(1):25.
PMID: 20226047 DOI: 10.1186/1756-9966-29-25

BACKGROUND: Giant cell tumor is an infrequent and unpredictable bony lesion. Although numerous attempts have been made to predict the behaviour of GCT, there are no definite biological or histological parameters to determine the prognosis or aggressiveness of this lesion
MATERIALS AND METHODS: We analyzed Ki 67 immuno-histochemistry of 31 consecutive cases staged III giant cell tumor to determine the clinico-pathological correlation. There were 19 male patients compare to 12 females. The mean age was 33.8 years ranged from 18 to 59 years. Five cases presented with local recurrence prior to wide resection and one case had multiple recurrences there after. Six cases had pulmonary metastases. Expression of Ki 67 antigen was evaluated by immuno-histochemical staining techniques using the avidin-biotin perioxidase complex method using an LSAB2 kit (Dako, Glostrup, Denmark). The primary antibody used in this study was Ki-67 (MIB-I clone, dilution 1:25; Dako).
RESULTS: The mean value of Ki-67 index obtained as a percentage of 1000 background cells was 8.15 (ranged 1.00 - 20.0). The median Ki 67 index was 7.5 with standard deviation of 5.12. The Ki 67 index of recurrence tumor was 4.323 compared to 6.05 without recurrence and was not statistically significant (mean difference of 0.865 with p value in independent t test of 0.736). The Ki 67 index was also not statistically significant in the presence of pulmonary metastases with the mean value of metastases group of 6.681 compared to 2.890 without metastases (mean difference of 1.895 with p value in independent t test of 0.424).
CONCLUSION: Ki 67 index is not use-full prognostic marker for aggressive type of giant cell tumor of the bone.

Matched MeSH terms: Ki-67 Antigen/analysis*
Inhibitory effects of Cinnamomum burmannii Blume stem bark extract and trans-cinnamaldehyde on nasopharyngeal carcinoma cells; synergism with cisplatin

Daker M, Lin VY, Akowuah GA, Yam MF, Ahmad M

Exp Ther Med, 2013 Jun;5(6):1701-1709.
PMID: 23837058

Nasopharyngeal carcinoma (NPC) is a malignancy that occurs in the epithelium of the nasopharynx. The standard treatment of NPC patients with locoregionally advanced stages is problematic and is often associated with toxicities. Therefore, it is essential to screen for naturally occurring compounds with strong apoptosis-inducing activity and minimal toxicity. This study investigated the effects of the standardized methanol extract of Cinnamomum burmannii Blume stem bark and its main constituent, trans-cinnamaldehyde (TCA), on human NPC cell lines. The content of TCA in C. burmannii methanol extract was standardized to be 13.61% w/w by means of gas chromatography-mass spectrometry (GC-MS). NPC cell proliferation was clearly inhibited within 24 h of treatment, with TCA exhibiting greater activity than the methanol extract. TCA was more active against NPC cells compared with cisplatin. There was a pronounced downregulation of the proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA) in the TCA-treated cells; while morphological observation indicated the induction of apoptosis. Caspase activation and prominent DNA damage, which are markers of apoptosis induction were detected. TCA demonstrated the ability to scavenge nitric oxide. The simultaneous combination of TCA and cisplatin produced synergistic anti-proliferative effects. Collectively, these data indicate the potential use of TCA for the treatment of NPC.

Matched MeSH terms: Ki-67 Antigen
Immunohistochemical detection of phospho-Akt, phospho-BAD, HER2 and oestrogen receptors alpha and beta in Malaysian breast cancer patients

Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M

Pathol Oncol Res, 2010 Jun;16(2):239-48.
PMID: 19882362 DOI: 10.1007/s12253-009-9216-3

Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.

Matched MeSH terms: Ki-67 Antigen/genetics; Ki-67 Antigen/metabolism
IFN-γ and IL-18 in conditioned media of parasite-infected host and IL-21-silenced colorectal cancer cells

Ge P, Ong CY, Abdalkareem AE, Khoo BY, Yuan B

Exp Ther Med, 2021 Feb;21(2):103.
PMID: 33335566 DOI: 10.3892/etm.2020.9535

The presence of certain soluble factors may provide a possible selective advantage for a parasite to gradually modify cell proliferation in neighbouring cells, which may result in chronic diseases. These soluble factors present in the conditioned medium also allow the parasite to invade rapidly into more host cells. The present study aimed to determine the levels of a group of type 1 T helper (Th1) cytokines in the conditioned media of host cells infected with parasites and in IL-21-silenced colorectal cancer cells. The conditioned media of human foreskin fibroblasts (HFFs) parasitized with the RH and ME49 strains of Toxoplasma gondii for 10 days were prepared, and subsequently the levels of the Th1 cytokines in the conditioned media were determined by ELISA. HFFs were incubated with the growth media containing selected soluble factors, and cell proliferation markers were subsequently analysed by reverse transcription-quantitative PCR. The mRNA expression level of cell proliferation markers was also examined in IL-21-silenced HCT116 cells, where the levels of soluble factors in the conditioned media were also determined as aforementioned. The results of the present study demonstrated that HFFs parasitized with ME49 released elevated levels of IFN-γ and lower levels of IL-18 into the conditioned medium compared with the controls. These phenomena were not observed in the conditioned medium of HFFs parasitized with RH. Similar levels of these soluble factors were also detected in the conditioned medium of IL-21-silenced HCT116 cells. The results of the present study also revealed that Ki67 and proliferating cell nuclear antigen mRNA expression was altered in host cells incubated with various levels of IFN-γ and IL-18, as well as in IL-21-silenced HCT116 cells compared with the respective controls. In conclusion, the current study provided preliminary evidence on the fundamental molecular mechanisms of host-parasite interactions that result in chronic diseases, which may aid in the treatment of these diseases in the relevant endemic regions.

Matched MeSH terms: Ki-67 Antigen
Expression of retinoblastoma protein and P16 proteins in classic Hodgkin lymphoma: relationship with expression of p53 and presence of Epstein-Barr virus in the regulation of cell growth and death

Kim LH, Peh SC, Poppema S

Hum Pathol, 2006 Jan;37(1):92-100.
PMID: 16360421

Deregulation of several genes involved in cell cycle control has been reported in classic Hodgkin lymphoma (cHL). This study aimed to investigate the expression of tumor suppressor proteins (P16(INK4A), retinoblastoma protein, and p53) in cHL in relation to the proliferation and apoptosis of Hodgkin/Reed-Sternberg (H/RS) cells, correlating with the status of Epstein-Barr virus (EBV). A total of 66 cHL cases and 10 nonneoplastic reactive lymphoid tissues were retrieved from the archives. Immunohistochemistry technique was used for the detection of protein expression. Presence of EBV infection was detected by EBV early RNA in situ hybridization. p16(INK4A) gene deletion status was assessed by fluorescence in situ hybridization technique. Expression of P16(INK4A) was observed in 49.2% of the cases, whereas positive retinoblastoma protein and p53 expressions in the H/RS cells were detected in 89.1% and 81.5% of the cases, respectively. Epstein-Barr virus positivity was detected in 53.0% of the cases. Proliferation marker, Ki-67 expression, was observed in 86.7% of the cases. There was no significant correlation between the expression of the various tumor suppressor proteins and Ki-67. Retinoblastoma protein and p53 were also not associated with the presence of EBV. An inverse relationship was observed between the expression of P16(INK4A) and the presence of EBV. There were no significant homozygous or hemizygous deletions of the p16(INK4A) gene. However, an aberrant copy number of chromosome 9 with the loss of one or more p16(INK4A) loci was detected in all cases assessable by fluorescence in situ hybridization. Loss of function of one or more tumor suppressor proteins may be involved in defective cell regulation of H/RS cells. Epstein-Barr virus may have a role in inhibiting P16(INK4A) expression, thus resulting in a perturbed p16(INK4A)-Rb cell cycle checkpoint.

Matched MeSH terms: Ki-67 Antigen/metabolism
Fulltext Expression of proliferating cell associated protein, Ki-67, supports cellular proliferation in WHO Class IV lupus nephritis

Cheah PL, Kunaseegaran R, Looi LM

Malays J Pathol, 2001 Jun;23(1):27-30.
PMID: 16329544

Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.

Matched MeSH terms: Ki-67 Antigen/metabolism*
Expression of p53, bcl-2 and Ki-67 in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix

Looi ML, Dali AZ, Ali SA, Ngah WZ, Yusof YA

Anal. Quant. Cytol. Histol., 2008 Apr;30(2):63-70.
PMID: 18561741

To assess the expression of p53, bcl-2 and Ki-67 in the progression of cervical neoplasia.

Matched MeSH terms: Ki-67 Antigen/metabolism*

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