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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: Lymph Nodes/pathology
MicroRNAs and Lymph Node Metastasis in Papillary Thyroid Cancers

Mutalib NS, Yusof AM, Mokhtar NM, Harun R, Muhammad R, Jamal R

Asian Pac J Cancer Prev, 2016;17(1):25-35.
PMID: 26838219

Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) has been shown to be associated with increased risk of locoregional recurrence, poor prognosis and decreased survival, especially in older patients. Hence, there is a need for a reliable biomarker for the prediction of LNM in this cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene translation or degradation and play key roles in numerous cellular functions including cell-cycle regulation, differentiation, apoptosis, invasion and migration. Various studies have demonstrated deregulation of miRNA levels in many diseases including cancers. While a large number of miRNAs have been identified from PTCs using various means, association of miRNAs with LNM in such cases is still controversial. Furthermore, studies linking most of the identified miRNAs to the mechanism of LNM have not been well documented. The aim of this review is to update readers on the current knowledge of miRNAs in relation to LNM in PTC.

Matched MeSH terms: Lymph Nodes/pathology
Fulltext Survival Analysis and Prognostic Factors for Colorectal Cancer Patients in Malaysia

Hassan MR, Suan MA, Soelar SA, Mohammed NS, Ismail I, Ahmad F

Asian Pac J Cancer Prev, 2016;17(7):3575-81.
PMID: 27510011

BACKGROUND: Cancer survival analysis is an essential indicator for effective early detection and improvements in cancer treatment. This study was undertaken to document colorectal cancer survival and associated prognostic factors in Malaysians.

MATERIALS AND METHODS: All data were retrieved from the National Cancer Patient Registry Colorectal Cancer. Only cases with confirmed diagnosis through histology between the year 2008 and 2009 were included. Retrieved data include sociodemographic information, pathological features and treatment received. Survival curves were plotted using the KaplanMeier method. Univariate analysis of all variables was then made using the Logrank test. All significant factors that influenced survival of patients were further analysed in a multivariate analysis using Cox' regression.

RESULTS: Total of 1,214 patients were included in the study. The overall 3 and 5year survival rates were 59.1% and 48.7%, respectively. Patients with localized tumours had better prognosis compared to those with advanced stage cancer. In univariate analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p=0.001) were found to be predictors of survival. None of the sociodemographic characteristics were found to exert any influence. In Cox regression analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p<0.001) were determined as independent prognostic factors of survival after adjusted for age, gender and ethnicity.

CONCLUSIONS: The overall survival rate for colorectal cancer patients in Malaysia is similar to those in other Asian countries, with staging at diagnosis, primary tumor size, involvement of lymph node and treatment modalities having significant effects. More efforts are needed to improve national survival rates in future.

Matched MeSH terms: Lymph Nodes/pathology
In regard to Wang et al on long-term outcomes following D2 gastrectomy for early gastric cancer

Tang WH

Asian Pac J Cancer Prev, 2015;16(7):3083.
PMID: 25854410
Matched MeSH terms: Lymph Nodes/pathology*
Prediction of lymph node involvement in patients with breast tumors measuring 3-5 cm in a middle-income setting: the role of CancerMath

Pijnappel EN, Bhoo-Pathy N, Suniza J, See MH, Tan GH, Yip CH, et al.

World J Surg, 2014 Dec;38(12):3133-7.
PMID: 25167896 DOI: 10.1007/s00268-014-2752-3

In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases.

Matched MeSH terms: Lymph Nodes/pathology*
Fulltext Lung adenocarcinoma with ipsilateral pleural and breast metastases

Liam CK, Pang YK, Kow KS

J Thorac Oncol, 2014 Jan;9(1):e8-9.
PMID: 24346108 DOI: 10.1097/01.JTO.0000438376.45132.9c
Matched MeSH terms: Lymph Nodes/pathology*
Comparative analysis between multilevel sectioning with conventional haematoxylin and eosin staining and immunohistochemistry for detecting nodal micrometastases with stage I and II colorectal cancers

Wong YP, Shah SA, Shaari N, Mohamad Esa MS, Sagap I, Isa NM

Asian Pac J Cancer Prev, 2014;15(4):1725-30.
PMID: 24641399

Management of patients with stage II colorectal carcinomas remains challenging as 20 - 30% of them will develop recurrence. It is postulated that these patients may harbour nodal micrometastases which are imperceptible by routine histopathological evaluation. The aims of our study were to evaluate (1) the feasibility of multilevel sectioning method utilizing haematoxylin and eosin stain and immunohistochemistry technique with cytokeratin AE1/AE3, in detecting micrometastases in histologically-negative lymph nodes, and (2) correlation between nodal micrometastases with clinicopathological parameters. Sixty two stage I and II cases with a total of 635 lymph nodes were reviewed. Five-level haematoxylin and eosin staining and one-level cytokeratin AE1/AE3 immunostaining were performed on all lymph nodes retrieved. The findings were correlated with clinicopathological parameters. Two (3.2%) lymph nodes in two patients (one in each) were found to harbour micrometastases detected by both methods. With cytokeratin AE1/AE3, we successfully identified four (6.5%) patients with isolated tumour cells, but none through the multilevel sectioning method. Nodal micrometastases detected by both multilevel sectioning and immunohistochemistry methods were not associated with larger tumour size, higher depth of invasion, poorer tumour grade, disease recurrence or distant metastasis. We conclude that there is no difference between the two methods in detecting nodal micrometastases. Therefore it is opined that multilevel sectioning is a feasible and yet inexpensive method that may be incorporated into routine practice to detect nodal micrometastases in centres with limited resources.

Matched MeSH terms: Lymph Nodes/pathology
Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma

Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, et al.

Hum Pathol, 2013 Mar;44(3):417-26.
PMID: 23026198 DOI: 10.1016/j.humpath.2012.06.007

The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.

Matched MeSH terms: Lymph Nodes/pathology*
Fulltext Cutaneous malignant melanoma: clinical and histopathological review of cases in a Malaysian tertiary referral centre

Pailoor J, Mun KS, Leow M

Malays J Pathol, 2012 Dec;34(2):97-101.
PMID: 23424771 MyJurnal

Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.

Matched MeSH terms: Lymph Nodes/pathology
Immunophenotyping analysis of lymph node biopsies by flow cytometry

Raja-Sabudin RZ, Hamid AA, Yusof N, Alauddin H, Aziz SA, Kulaveerasingam S, et al.

Saudi Med J, 2012 Oct;33(10):1131-3.
PMID: 23047221
Matched MeSH terms: Lymph Nodes/pathology*
Tuberculous cervical lymphadenitis in a patient with suspected neck recurrence

Yong DJ, Iskandar H, Razif MY

Chin Med J (Engl), 2012 May;125(9):1667-8.
PMID: 22800842

The significance of metastastic disease in the cervical lymph nodes has long been appreciated. The rich lymphatics of the upper aerodigestive tract explained the high incidence of cervical metastasis, occasional bilaterally spread. Even with appropriate treatment, cervical recurrences do occur. Nonetheless, with the resurgence of tuberculosis, the differential of tuberculous cervical lymphadenitis should be excluded. Appropriate modalities should be employed in making the appropriate diagnosis possible.

Matched MeSH terms: Lymph Nodes/pathology*
Fulltext Ethnic differences in survival after breast cancer in South East Asia

Bhoo-Pathy N, Hartman M, Yip CH, Saxena N, Taib NA, Lim SE, et al.

PLoS One, 2012;7(2):e30995.
PMID: 22363531 DOI: 10.1371/journal.pone.0030995

The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia.

Matched MeSH terms: Lymph Nodes/pathology
Who are the breast cancer survivors in Malaysia?

Ibrahim NI, Dahlui M, Aina EN, Al-Sadat N

Asian Pac J Cancer Prev, 2012;13(5):2213-8.
PMID: 22901196

INTRODUCTION: Worldwide, breast cancer is the commonest cause of cancer death in women. However, the survival rate varies across regions at averages of 73%and 57% in the developed and developing countries, respectively.
OBJECTIVE: This study aimed to determine the survival rate of breast cancer among the women of Malaysia and characteristics of the survivors.
METHOD: A retrospective cohort study was conducted on secondary data obtained from the Breast Cancer Registry and medical records of breast cancer patients admitted to Hospital Kuala Lumpur from 2005 to 2009. Survival data were validated with National Birth and Death Registry. Statistical analysis applied logistic regression, the Cox proportional hazard model, the Kaplan-Meier method and log rank test.
RESULTS: A total of 868 women were diagnosed with breast cancer between January 2005 and December 2009, comprising 58%, 25% and 17% Malays, Chinese and Indians, respectively. The overall survival rate was 43.5% (CI 0.573-0.597), with Chinese, Indians and Malays having 5 year survival rates of 48.2% (CI 0.444-0.520), 47.2% (CI 0.432-0.512) and 39.7% (CI 0.373-0.421), respectively (p<0.05). The survival rate was lower as the stages increased, with the late stages were mostly seen among the Malays (46%), followed by Chinese (36%) and Indians (34%). Size of tumor>3.0cm; lymph node involvement, ERPR, and HER 2 status, delayed presentation and involvement of both breasts were among other factors that were associated with poor survival.
CONCLUSIONS: The overall survival rate of Malaysian women with breast cancer was lower than the western figures with Malays having the lowest because they presented at late stage, after a long duration of symptoms, had larger tumor size, and had more lymph nodes affected. There is an urgent need to conduct studies on why there is delay in diagnosis and treatment of breast cancer women in Malaysia.

Matched MeSH terms: Lymph Nodes/pathology
Fulltext Does the axillary lymph node ratio have any added prognostic value over pN staging for South East Asian breast cancer patients?

Saxena N, Hartman M, Yip CH, Bhoo-Pathy N, Khin LW, Taib NA, et al.

PLoS One, 2012;7(9):e45809.
PMID: 23029254 DOI: 10.1371/journal.pone.0045809

Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed.

Matched MeSH terms: Lymph Nodes/pathology*
Cyclin D1 amplification in tongue and cheek squamous cell carcinoma

Mahdey HM, Ramanathan A, Ismail SM, Abraham MT, Jamaluddin M, Zain RB

Asian Pac J Cancer Prev, 2011;12(9):2199-204.
PMID: 22296356

INTRODUCTION: Several molecular markers have been studied for their usefulness as prognostic markers in oral squamous cell carcinoma (OSCC). One such molecular marker is cyclin D1 which is a proto-oncogene located on 11q13 in humans.
OBJECTIVE: To explore the feasibility of using cyclin D1 as a prognostic marker in tongue and cheek SCC by the fluorescent-in-situ hybridization (FISH) method.
METHODS: Fifty paraffin-embedded samples (25 each of cheek and tongue SCCs) were obtained from the archives of the Oral Pathology Diagnostic Laboratory. Sociodemographic data, histopathologic diagnoses, lymph node status and survival data were obtained from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS)coordinated by the Oral Cancer Research and Coordinating Centre (OCRCC), University of Malaya. The FISH technique was used to detect the amplification of cyclin D1 using the Vysis protocol. Statistical correlations of cyclin D1 with site and lymph node status were analyzed using the Fisher exact test. Kaplan-Meier and Log Rank (Mantel-Cox) test were used to analyze cyclin D1 amplification and median survival time.
RESULTS: Positive amplification of cyclin D1 was detected in 72% (36) of OSCCs. Detection of positive amplification for cyclin D1 was observed in 88% (22) and 56% (14) of the tongue and cheek tumors, respectively, where the difference was statistically significant (P=0.012). Lymph node metastasis of cheek SCCs showed a trend towards a significant association (P= 0.098) with cyclin D1 amplification whereas the lymph node metastasis of tongue SCC was clearly not significant (P=0.593).There was a statistically significant correlation between cyclin D1 positivity and survival rate (P=0.009) for overall SCC cases and (P<0.001) for cheek SCC cases.
CONCLUSION: The present study found that cyclin D1 amplification may differ in different subsites of OSCC (tongue vs cheek) and its positive amplification implies an overall poor survival in OSCCs, particularly those arising in cheeks.

Matched MeSH terms: Lymph Nodes/pathology
Fulltext Dendritic cell distribution in lymphomas

Hussin HN, Zulkifli FN, Phang KS, Cheong SK

Malays J Pathol, 2009 Dec;31(2):105-12.
PMID: 20514853 MyJurnal

Dendritic cells (DC) are specialized antigen presenting cells (APC) that have important roles in host defenses and in generating anti-tumour immune response. Altered frequency and maturation of DC have been reported in malignant tumours. We studied the distribution and maturation status of DC by immunohistochemistry, on the formalin-fixed, paraffin-embedded lymph node tissues of 32 histologically diagnosed lymphomas and 40 inflammatory conditions that were retrieved from the Department of Pathology, UKM Medical Centre, Kuala Lumpur. Our study showed a significant reduction in the total DC counts in the lymphoma tissues compared to the inflammatory conditions. The mature and immature DC counts were both significantly reduced (p = 0.008 and 0.001 respectively), although a greater reduction was observed in mature DC numbers. We also observed compartmentalization of DC where the immature DC were seen within the tumour tissues and the mature DC were more in peri-tumoural areas. Our findings were similar to other reports, suggesting that reduced numbers of DC appears to be a factor contributing to lack of tumour surveillance in these cases.

Matched MeSH terms: Lymph Nodes/pathology*
Fulltext A case report of adult T-cell leukaemia/lymphoma

Shanmugam H, Eow GI, Nadarajan VS

Malays J Pathol, 2009 Jun;31(1):63-6.
PMID: 19694316 MyJurnal

Adult T-cell leukaemia/lymphoma (ATLL) is a rare T lymphoproliferative disorder which is aetiologically linked with human T-cell lymphotropic virus type-1 (HTLV-1). HTLV-1 is endemic in Japan, Caribbean and Africa. The highest incidence of ATLL is in Japan although sporadic cases have been reported elsewhere in the world. We describe a case of ATLL with an unusual presentation which we believe is the first reported case of ATLL in Malaysia based on our literature search. A 51-year-old Indian lady was referred to University Malaya Medical Centre for an incidental finding of lymphocytosis while being investigated for pallor and giddiness. Clinical examination revealed bilateral shotty cervical lymph nodes with no hepato-splenomegaly or skin lesions. Laboratory investigations showed absolute lymphocytosis (38 x 10(9)/L) with a mildly increased serum lactate dehydrogenase. The peripheral blood smear showed the presence of predominantly small to medium sized, non-flower lymphocytes. The bone marrow showed similar findings of prominent lymphocytosis. Immunophenotyping of the bone marrow mononuclear cells showed CD3+, CD4+, CD5+, CD7- and CD25+ which is characteristic of ATLL phenotype. HTLV-1 infection was confirmed by the presence of HTLV-1 proviral DNA in the tumor cells using conventional Polymerase Chain Reaction (PCR) and real-time PCR. Here, we discuss the pathogenesis and characteristics of ATLL as well as the detection of HTLV-1 by real time PCR.

Matched MeSH terms: Lymph Nodes/pathology
Feline parvovirus infection in an Asian palm civet (Paradoxurus hermaphroditus)

Demeter Z, Gál J, Palade EA, Rusvai M

Vet Rec, 2009 Feb 14;164(7):213-6.
PMID: 19218594
Matched MeSH terms: Lymph Nodes/pathology
Predictors of axillary lymph node metastases in breast cancer: is there a role for minimal axillary surgery?

Yip CH, Taib NA, Tan GH, Ng KL, Yoong BK, Choo WY

World J Surg, 2009 Jan;33(1):54-7.
PMID: 18958521 DOI: 10.1007/s00268-008-9782-7

Axillary nodal status is one of the most important prognostic factors in breast cancer. In the present study we used it to determine the predictors of axillary lymph node metastases in breast cancer and to determine if there is a group of patients in whom minimal axillary surgery is indicated.

Matched MeSH terms: Lymph Nodes/pathology*
Follicular dendritic cell sarcoma of inguinal lymph node--a case report

Pailoor J, Iyengar KR, Chan KS, Sumithra S

Malays J Pathol, 2008 Dec;30(2):115-9.
PMID: 19291921

Follicular dendritic cell sarcomas (FDCS) are rare neoplasms that involve lymph nodes or extranodal sites. They show varied histological features and thus can be mistaken for carcinoma or sarcoma. Correct identification is important for further management. A 43-year-old Indian female presented with a three-month history of progressive swelling at the right inguinal region. It was excised completely and was reported as lymph node with metastatic poorly differentiated carcinoma based on Haematoxylin and eosin (H&E) stain findings. Computerized tomography (CT) scans of thorax, abdomen and pelvis were normal and did not reveal a primary site. Following this, the case was referred to one of the authors. The slides were reviewed and a variety of immunocytochemical markers were done. The tumour cells were negative for epithelial, melanocytic, neural, leucocyte and soft tissue tumour markers. They were immunopositive for CD21, CD35 and negative for CD68. Based on the immunocytochemical findings, a final diagnosis of FDCS was made. This case highlights the histological and immunophenotypical profile of a rare tumour which requires a high index of suspicion for diagnosis.

Matched MeSH terms: Lymph Nodes/pathology*

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