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Clinical usefulness of tumour markers

Lai LC, Cheong SK, Goh KL, Leong CF, Loh CS, Lopez JB, et al.

Malays J Pathol, 2003 Dec;25(2):83-105.
PMID: 16196365

Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.

Matched MeSH terms: Biomarkers, Tumor/metabolism*
Fulltext The clinical significance of elevated levels of serum CA 19-9

Pavai S, Yap SF

Med J Malaysia, 2003 Dec;58(5):667-72.
PMID: 15190651

The tumour marker CA19-9 is a sensitive marker for pancreatic, gastric and hepatobiliary malignancies. High CA 19-9 level indicates unresectable lesions and a poor prognosis. The objective of the study was to determine the significance and implications of elevated CA 19-9 levels in the serum. A one-year retrospective review of all patients who had CA19-9 measured in our Medical Centre was undertaken; 69 patients were found to have CA 19-9 level above the cut-off value (37 U/ml). Thirty-six patients had malignant and the remaining 33 had benign lesions. CA 19-9 was found to be elevated in malignancies of pancreas, colorectum, lung, liver and ovary. Benign conditions associated with elevation of CA 19-9 included disease of the hepatobiliary system, pneumonia, pleural effusion, renal failure and SLE. In two individuals, there was no obvious cause for the elevation of this marker. CA 19-9 levels were significantly lower in benign than in malignant conditions. In conclusion, elevated CA 19-9 may be found in patients with benign as well as malignant disease. Therefore, it is important (1) that elevated levels of CA 19-9 are interpreted in the light of the clinical presentation of the patient and (2) to be aware of the benign conditions that can be associated with increased levels of this marker. With these factors in mind, CA 19-9 can be used to assist in the diagnosis of pancreatic cancer and assessment of resection adequacy post-operatively.

Matched MeSH terms: Biomarkers, Tumor/blood*
Telomerase activity in Malaysian patients with central nervous system tumors

Isa MN, Sulong S, Sidek MR, George PJ, Abdullah JM

Southeast Asian J. Trop. Med. Public Health, 2003 Dec;34(4):872-6.
PMID: 15115103

Telomerase, the enzyme that stabilizes telomere length is reactivated with almost all cancer types, and may be a useful diagnostic marker for malignancy. Telomerase activity has been detected in germ line cells and most cancer cells, whereas most normal somatic cells have no clearly detectable telomerase activity. In our study, we aim to detect telomerase activity in 20 human central nervous system tumors from Malaysian patients. Telomerase activity was detected based on a highly sensitive procedure consisting of a CHAPS detergent-based extraction from frozen tissues and a PCR-based telomeric repeat amplification protocol (TRAP) using a TRAPEZE Telomerase Detection Kit (Intergen, Co). Telomerase activity was considered positive when a ladder of products was observed starting at 50bp, with 6bp increments. The activity was detected in 30% of the samples analysed, included glioblastoma multiforme, meduloblastoma, paraganglioma and oligodendroglioma. The result of Fisher's exact test indicated that there was a significant association between telomerase activity status with tumor grade (p=0.003). These results suggest that telomerase activity may be an important marker for tumor malignancy.

Matched MeSH terms: Biomarkers, Tumor/metabolism*
Evaluation of a new biopsy urease test: Pronto Dry, for the diagnosis of Helicobacter pylori infection

Said RM, Cheah PL, Chin SC, Goh KL

Eur J Gastroenterol Hepatol, 2004 Feb;16(2):195-9.
PMID: 15075994

BACKGROUND: The gastric biopsy urease test is the most frequently used test for the diagnosis of Helicobacter pylori infection in routine gastrointestinal endoscopy practice. In Malaysia up to recently, only one commercial biopsy urease test was available: the CLO test (Ballard Medical Products, Draper, Utah, USA). Large endoscopy units use their own 'homemade' unbuffered ultra rapid urease test for diagnosis of H. pylori infection.
OBJECTIVE: To compare the accuracy and reaction time of a new biopsy urease test, Pronto Dry (Medical Instruments Corporation, Solothurn, Switzerland) and the CLO test in the diagnosis of H. pylori infection.
METHODS: Consecutive patients presenting with dyspepsia to the endoscopy unit, University of Malaya Medical Centre were recruited for the study. Patients who were previously treated for H. pylori infection or who had received antibiotics, proton pump inhibitors or bismuth compounds in the preceding 4 weeks were excluded. H. pylori diagnosis was made based on the ultra rapid urease test and histological examination of gastric biopsies. Four antral and four corpus biopsies were taken for this purpose from all patients. A diagnosis of H. pylori infection was made when both the ultra rapid urease test and histology were positive in either the antral or corpus biopsies. A negative diagnosis of H. pylori was made when both tests from antral and corpus biopsies were all negative. Another four antral and four corpus biopsies (two each) were taken for the Pronto Dry and CLO tests. The Pronto Dry and CLO tests were stored and performed according to the manufacturer's instruction.
RESULTS: Two hundred and eight patients were recruited in the study. Eighty-six of the patients were males and 122 were females. The mean age was 46.3 years with a range of 15-82 years. The results for both the Pronto Dry and the CLO tests were completely concordant with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 98.1%, 100%, 100%, 98.1% and 99%, respectively. The Pronto Dry test showed a faster reaction time to positive compared with the CLO test, with 96.2% positive reaction by 30 min versus 70.8% and 100% positive reaction time by 55 min versus 83%. The colorimetric change was also more distinct with the Pronto Dry test compared with the CLO test.
CONCLUSIONS: Both the Pronto Dry and the CLO tests were highly accurate for the diagnosis of H. pylori infection. The Pronto Dry test showed a quicker positive reaction time and the positive colour change was more distinct.

Matched MeSH terms: Biomarkers/analysis
Hev b 5 and Hev b 13 as allergen markers to estimate the allergenic potency of latex gloves

Yeang HY, Arif SA, Raulf-Heimsoth M, Loke YH, Sander I, Sulong SH, et al.

J Allergy Clin Immunol, 2004 Sep;114(3):593-8.
PMID: 15356563 DOI: 10.1016/j.jaci.2004.05.039

BACKGROUND:
Sensitization to natural rubber latex has been linked to proteins from medical latex gloves. Various assays to estimate the amount of residual allergenic proteins extractable from latex gloves to assess their potential exposure hazard have inherent weaknesses.

OBJECTIVE:
This investigation was aimed at developing 2-site immunoenzymetric assays and identifying appropriate protein markers to assess the allergenic potential of latex gloves.

METHODS:
The presence of 6 latex allergens--Hev b 1, 2, 3, 5, 6, and 13--was measured in a cross-section of commercial latex medical gloves by using monoclonal and polyclonal antibody-based 2-site immunoenzymetric assays. The overall allergenic potential of these gloves was assessed by IgE-inhibition assay. Stepwise multiple regression analyses were performed to identify marker allergens that best explained the variation in latex glove allergenicity.

RESULTS:
All 6 latex allergens were detected in at least some of the glove samples. Hev b 5 and Hev b 13 were identified as the marker allergens that combined best to explain the variation in the glove allergenicity. The significant multiple correlation (R=0.855) between these 2 markers and glove allergenic potency forms the basis of an assay to gauge latex glove allergenicity.

CONCLUSION:
The overall allergenic potential of latex gloves can be estimated by using Hev b 5 and Hev b 13 as indicator allergens. The correlation between glove allergenicity and the level of these allergens was maintained for low-protein gloves (<200 microg/g). This estimation of glove allergenicity was superior to that obtained by using total protein readings.

Matched MeSH terms: Biomarkers/analysis
Fulltext The prognostic value of C-reactive protein (CRP) levels in patients with acute ischaemic stroke

Hamidon BB, Sapiah S, Nawawi H, Raymond AA

Med J Malaysia, 2004 Dec;59(5):631-7.
PMID: 15889566 MyJurnal

Increasing evidence suggests that inflammation plays an important role in the development of both cardiovascular and cerebrovascular events. Recently C-reactive protein (CRP) levels have been reported to be a prognostic factor for cerebrovascular and cardiovascular events. The main objective of the study was to evaluate the prognostic value of CRP levels in a first ever ischaemic stroke at one month. All ischaemic stroke patients who were admitted to Hospital Universiti Kebangsaan Malaysia (HUKM) between May 2002 and July 2002 were eligible for the study. CRP levels were taken within 72 hours after an acute ischaemic stroke. The functional ability was assessed using the Barthel Index (BI) after one month of stroke. During the study period 84 patients were admitted to HUKM with the diagnosis of ischaemic stroke; 49 patients were enrolled and 35 were excluded. Twenty-nine patients (59.2%) had elevated CRP levels (median 1.64+/-3.07 mg/dL, range 0.06 to 16.21 mg/dL). Elevated CRP levels were found to be a predictor of severe functional disability (BI<5) and were also associated with larger infarcts. In conclusion, elevated CRP levels are associated with poorer functional outcome and predict a larger infarct size.

Matched MeSH terms: Biomarkers/blood
Potential anticancer effect of red spinach (Amaranthus gangeticus) extract

Sani HA, Rahmat A, Ismail M, Rosli R, Endrini S

Asia Pac J Clin Nutr, 2004;13(4):396-400.
PMID: 15563447

The objective of this study was to determine the anti cancer effects of red spinach (Amaranthus gangeticus Linn) in vitro and in vivo. For in vitro study, microtitration cytotoxic assay was done using 3-(4,5-dimethylthiazol-2-il)-2,5-diphenil tetrazolium bromide (MTT) kit assay. Results showed that aqueous extract of A gangeticus inhibited the proliferation of liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). The IC(50) values were 93.8 mu g/ml and 98.8 mu g/ml for HepG2 and MCF-7, respectively. The inhibitory effect was also observed in colon cancer cell line (Caco-2), but a lower percentage compared to HepG2 and MCF-7. For normal cell line (Chang Liver), there was no inhibitory effect. In the in vivo study, hepatocarcinogenesis was monitored in rats according to Solt and Farber (1976) without partial hepatectomy. Assay of tumour marker enzymes such as glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), uridyl diphosphoglucuronyl transferase (UDPGT) and alkaline phosphatase (ALP) were carried out to determine the severity of hepatocarcinogenesis. The result found that supplementation of 5%, 7.5% and 10% of A. gangeticus aqueous extract to normal rats did not show any significant difference towards normal control (P <0.05). The exposure of the rats to chemical carcinogens diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) showed a significant increase in specific enzyme activity of GGT, GST, UDPGT and ALP compared to normal control (P <0.05). However, it was found that the supplementation of A. gangeticus aqueous extract in 5%, 7.5% and 10% to cancer-induced rats could inhibit the activity of all tumour marker enzymes especially at 10% (P <0.05). Supplementation of anti cancer drug glycyrrhizin at suggested dose (0.005%) did not show any suppressive effect towards cancer control (P <0.05). In conclusion, A. gangeticus showed anticancer potential in in vitro and in vivo studies.

Matched MeSH terms: Biomarkers, Tumor/metabolism
Are plasma insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) useful markers of prostate cancer?

Lopez JB, Sahabudin RM, Chin LP

Int. J. Biol. Markers, 2004 Apr-Jun;19(2):164-7.
PMID: 15255551

Increased concentrations of insulin-like growth factor I (IGF-I) and decreased insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been proposed as markers of prostate cancer (CaP). The evidence for this, however, is contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3 ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/- 36.1 ng/mL; n=46), but the differences between the three groups were not statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p = 0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL; n=59), but the difference between the two groups of patients was not significant (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001). Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0 ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were 76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA for CaP detection.

Matched MeSH terms: Biomarkers, Tumor/blood*
Effect of cacao liquor extract on tumor marker enzymes during chemical hepatocarcinogenesis in rats

Amin I, Koh BK, Asmah R

J Med Food, 2004;7(1):7-12.
PMID: 15117546

This study investigated the effect of cacao liquor extract (CLE) on tumor marker enzymes--alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities--in plasma and/or liver of hepatocarcinogenic rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. Twenty-nine male Sprague-Dawley rats (weighing 150-330 g) were divided into four groups (n = 6-8): normal control group (N), normal group + CLE (NE), cancer group (C), and cancer group + CLE (CE). Analysis of variance showed significant differences (P

Matched MeSH terms: Biomarkers, Tumor/blood
Low prevalence of autoimmune diabetes markers in a mixed ethnic population of Singaporean diabetics

Todd AL, Ng WY, Lui KF, Thai AC

Intern Med J, 2004 Jan-Feb;34(1-2):24-30.
PMID: 14748910 DOI: 10.1111/j.1444-0903.2004.00482.x

BACKGROUND: Circulating antibodies to glutamic acid decarboxylase (GADab) and tyrosine phosphatase-like molecule IA-2 (IA-2ab) are major indicators for auto-immune destruction of pancreatic islet cells. They identify a majority of Caucasians with type 1 diabetes and approximately 50% of Asians, providing evidence of an idiopathic aetiology in the latter. The present study investigated these autoantibodies in a mixed ethnic group.
METHODS: Hospital clinic patients with clinically defined type 1 (n = 93) and type 2 (n = 300) diabetes and representing Singapore's major ethnic groups--Chinese, Indians and Malays--were studied. GADab and IA-2ab frequencies, and association of autoimmunity status with clinical and biochemical profiles were analysed.
RESULTS: Radio-immunoprecipitation assays detected either or both antibodies (seropositivity) in 41.9% of subjects with type 1 diabetes. GADab was detected in 36.6% and IA-2ab in 23.7% of type 1 diabetics. Prevalence of IA-2ab showed a reduction in frequency with disease duration (P = 0.026). In clinical type 2 diabetics, seropositivity was 10.0% with higher frequency in Malays (17.5%) than Chinese (9.7%) and Indians (4.5%). Multivariate analysis revealed that low fasting C-peptide was associated with seropositivity (odds ratio (OR) = 0.15; 95% confidence interval (CI) = 0.04-0.58). A significant relationship (OR = 13.5; 95% CI = 5.0-36.7) between insulin requirement and duration (>5 years) was also revealed. In patients with type 2 diabetes there was a trend of gradual progression to insulin dependency. However, there was considerable variation in body mass index between ethnic subgroups of type 2 diabetics, particularly for Chinese (mean (SD) = 26.0 (4.7)) and Malays (mean (SD) = 29.2 (5.9); P < 0.001).
CONCLUSIONS: Presence of both antibodies in our mixed ethnic group of type 1 diabetes patients was much lower than in Caucasians. Significant numbers of patients were seronegative for antibodies. Influences due to ethnicity and adiposity would require further investigations.

Matched MeSH terms: Biomarkers/blood*
Epstein-Barr virus serology in the diagnosis of nasopharyngeal carcinoma

Wong MM, Lye MS, Cheng HM, Sam CK

Asian Pac J Allergy Immunol, 2005 Mar;23(1):65-7.
PMID: 15997877

The antibody levels to viral capsid antigen (VCA) and early antigen (EA) of Epstein-Barr virus (EBV) in 164 nasopharyngeal carcinoma (NPC) patients from Sarawak, East Malaysia were significantly higher than those in 147 sex, age and ethnically matched healthy controls. As diagnostic markers of NPC, IgG/VCA at reciprocal titers > or =160 was the most sensitive (89%, with 98% specificity), while IgA/EA at > or =5 was the most specific (100%) but the least sensitive (75%). The sensitivity and specificity of IgA/VCA at reciprocal titers > or =10 were 84% and 97%. IgA/VCA has an advantage over IgG/VCA despite the slightly lower sensitivity due to its consistently more distinct fluorescence reaction. The sensitivity and specificity can be marginally improved by a combination of two tests.

Matched MeSH terms: Biomarkers, Tumor/blood
Fulltext A combined case of macroprolactinoma, growth hormone excess and Graves' disease

Hussein Z, Tress B, Colman PG

Med J Malaysia, 2005 Jun;60(2):232-6.
PMID: 16114168

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

Matched MeSH terms: Biomarkers/blood
Interpretation and application of virological testing including resistance in chronic hepatitis B

Locarnini S

Med J Malaysia, 2005 Jul;60 Suppl B:41-51.
PMID: 16108173
Matched MeSH terms: Biomarkers/blood
Surrogate markers for liver fibrosis

Poynard T

Med J Malaysia, 2005 Jul;60 Suppl B:39-40.
PMID: 16108172
Matched MeSH terms: Biomarkers*
Clinicopathologic and immunohistochemical differences in complete and partial hydatidiform moles in a multiracial Malaysian population

Hayati AR, Tan GC

Int J Gynecol Pathol, 2005 Jul;24(3):277-85.
PMID: 15968205
Matched MeSH terms: Biomarkers, Tumor/biosynthesis*
Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patients

Kuppusamy UR, Indran M, Rokiah P

Diabet Med, 2005 Oct;22(10):1343-6.
PMID: 16176194 DOI: 10.1111/j.1464-5491.2005.01630.x

Aims: Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant-antioxidant levels in these patients.

Methods: Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods.

Results: Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA(1c), fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant-antioxidant parameters as a function of HbA(1c) in each ethnic group revealed a strong association of HbA(1c) with oxidative indices.

Conclusions: The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA(1c) remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration.

Matched MeSH terms: Biomarkers/blood
RET and p53 expression in thyroid follicular adenoma: a study of 52 cases with 14 years follow-up

Othman NH, Omar E, Mahmood MH, Madhavan M

Malays J Pathol, 2005 Dec;27(2):91-8.
PMID: 17191391

Most previous studies on RET and p53 proteins have focused on thyroid papillary carcinoma. We investigated the role of RET and p53 protein expressions using immunohistochemistry on 52 cases of thyroid follicular adenomas and studied the follow-up records of these patients. The range of follow-up period was 3 to 14 years. The patients were between 15 and 71 years of age with a median age of 34.5 years. There were 46 females and 6 males. Except for 3 cases, all patients were Malays. The minimum volume of the tumour was 1000 mm3 and the maximum was 512,000 mm3 with a median of 270,000 mm3. Eleven (21.2%) cases showed RET expression. RET expression was not statistically significant when cross-tabulated against sex (p = 0.322), ethnicity (p = 0.518), age (p = 0.466) and symptom duration (p = 0.144). Six (11.5%) of 52 cases showed p53 immunopositivity. p53 expressions were also not significantly correlated to the clinical parameters above. There was no correlation between RET and p53 protein expressions. The only statistically significant finding was the association of tumour volume with duration of symptoms (p = 0.05). All patients are alive at the time of writing. 3 had recurrent goitre, 2 of these were diagnosed as colloid goitre while the third was a follicular lesion. One patient suffered from depression requiring anti-depressant treatment. In conclusion, unlike papillary carcinoma in which the roles of ret and p53 oncogenes are known, their roles in influencing the behaviour of follicular adenoma has not been ascertained.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Human telomerase reverse transcriptase expression in oral carcinogenesis--a preliminary report

Kumar SK, Zain RB, Ismail SM, Cheong SC

J Exp Clin Cancer Res, 2005 Dec;24(4):639-46.
PMID: 16471328

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is strongly associated with telomerase activity implicated in cellular immortalization and tumorigenesis. In situ detection of hTERT will aid in determining the localization of telomerase positive cells. The aim of this study was to detect hTERT protein expression in multistep oral carcinogenesis using paraffin embedded tissue samples, and to study the relationship of hTERT expression with different histological stages in oral carcinogenesis. Normal (n = 4), hyperplastic (n = 4), dysplastic (n = 4) and neoplastic (n = 10) oral epithelia representing different histological stages in oral carcinogenesis were included in the study. hTERT protein detection was done by immunohistochemistry (IHC) technique. Nuclear staining intensities were noted and the hTERT-labelling index was determined. Dysplastic and neoplastic oral epithelia showed an increased percentage of hTERT positive cells (Grade 4: > 50% positive staining nuclei) with intense staining in the basal, parabasal and superficial layers of the epithelia, unlike normal oral mucosa which showed intense staining only in the basal and parabasal cell layers, which are the normal proliferative progenitor compartments. hTERT protein expression was elevated with the corresponding advancement of the histological stages of oral carcinogenesis, from normal to hyperplasia to dysplasia to carcinoma. There seems to be an upregulation of hTERT protein expression during the progression of oral cancer, therefore, this may indicate the feasibility of IHC detection of hTERT protein in oral carcinogenesis as a potential diagnostic or prognostic marker.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Cytologic evaluation of prognostic markers in breast carcinoma

Jayaram G, Elsayed EM

Acta Cytol., 2005 Nov-Dec;49(6):605-10.
PMID: 16450899

To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and correlate the results with histologic typing, to grade breast carcinoma on FNAC material and correlate the findings with Bloom-Richardson histologic grading, and to determine the estrogen receptor (ER) status in cases of breast carcinoma by immunocytochemical (ICC) staining of FNA cytologic material and correlate the findings with ER status, as determined by immunohistochemical (IHC) staining of tissue sections.

STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed on FNAC formed the basis of this study. Typing was done in all cases on the basis of cytologic features and grading in 62. (Fifteen cases were special types of breast carcinoma). In all cases, ER status was determined by immunostaining of cytologic smears. Results of tumor typing, grading and ER status on cytologic material were compared with the results of histologic typing, grading and immunostaining of histologic material obtained from mastectomy or wide excision specimens.

RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen of 18 cases that were cytologically grade 3 were confirmed on histology, while 3 proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases were confirmed on histology while 1 was grade 2. The overall accuracy for cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology, while in 2 cases the cellularity of the cytologic smear was insufficient to assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that was inadequate for assessment of ER. Sensitivity and specificity rates for ER detection on ICC were 97.4% and 74.3%, respectively.

CONCLUSION: Tumor typing, grading and evaluation of ER status on FNA C material in breast carcinomas are simple, quick and moderately reliable techniques that compare and correlate favorably with histologic typing, grading and ER status on IHC.

Matched MeSH terms: Biomarkers, Tumor/analysis*
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: Biomarkers, Tumor/metabolism

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