Ki67 index in breast cancer: correlation with other prognostic markers and potential in pakistani patients.

INTRODUCTION: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. METHODS: A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. RESULTS: Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. CONCLUSION: Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification.

Accuracy of frozen section analysis of sentinel lymph nodes for the detection of Asian breast cancer micrometastasis - experience from Pakistan.

BACKGROUND: Intraoperative sentinel lymph node biopsy has now become the standard of care for patients with clinically node negative breast cancer for diagnosis and also in order to determine the need for immediate axillary clearance. Several large scale studies confirmed the diagnostic reliability of this method. However, micrometastases are frequently missed on frozen sections. Recent studies showed that both disease free interval and overall survival are significantly affected by the presence of micrometastatic disease. The aim of this study was to determine the sensitivity and specificity of intraoperative frozen section analysis of sentinel lymph nodes (SLNs) for the detection of breast cancer micrometastasis and to evaluate the status of non-sentinel lymph nodes (non-SLNs) in those patients subjected to further axillary sampling. MATERIALS AND METHODS: We performed a retrospective study on 154 patients who underwent SLN biopsy from January 2008 till October 2011. The SLNs were sectioned at 2 mm intervals and submitted entirely for frozen sections. Three levels of each section submitted are examined and the results were compared with further levels on paraffin sections. RESULTS: Overall 40% of patients (62/154) were found to be SLN positive on final (paraffin section) histology, out of which 44 demonstrated macrometastases (>2mm) and 18 micrometastases (<2mm). The overall sensitivity and specificity of frozen section analysis of SLN for the detection of macrometastasis was found to be 100% while those for micrometastasis were 33.3% and 100%, respectively. Moreover 20% of patients who had micrometastases in SLN had positive non-SLNs on final histology. CONCLUSIONS: Frozen section analysis of SLNs lacks sufficient accuracy to rule out micrometastasis by current protocols. Therefore these need to be revised in order to pick up micrometastasis which appears to have clinical significance. We suggest that this can be achieved by examining more step sections of blocks.