The Predictive and Prognostic Role of Topoisomerase IIα and Tissue Inhibitor of Metalloproteinases 1 Expression in Locally Advanced Breast Carcinoma of Egyptian Patients Treated With Anthracycline-based Neoadjuvant Chemotherapy.

PURPOSE: Locally advanced breast cancer (LABC) is a heterogeneous entity that remains a clinical challenge. Anthracycline-based neoadjuvant chemotherapy has emerged as the standard of care for those patients. However, it is associated with serious side effects including cardiotoxicity. This study aimed to evaluate the prognostic and predictive role of topoisomerase IIα (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in Egyptian LABC patients after anthracycline-based neoadjuvant chemotherapy. MATERIALS AND METHODS: This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of TOP2α and TIMP-1 was evaluated in pretreatment needle core biopsies. Results were correlated with clinicopathlogic parameters, response to neoadjuvant chemotherapy in postoperative specimens, disease-free survival and overall survival (OS). RESULTS: Positive TOP2α expression was detected in 57/84 (67.9%) cases. It was significantly associated with good response to chemotherapy in breast (P=0.048) and lymph node (P=0.06) as well as prolonged OS (P=0.04). It tended to be the most independent prognostic factor for OS (P=0.06). Positive TIMP-1 expression was detected in 48/84 (57.1%) cases. It was significantly associated with poor response to chemotherapy in breast (P=0.02). The 2T profile (TOP2α+ and TIMP-1-) was significantly associated with good response to chemotherapy in breast (P=0.006). CONCLUSION: TOP2α and TIMP-1 are important predictive and prognostic factors in LABC patients who received anthracycline-based chemotherapy.

The prognostic and predictive significance of PARP-1 in locally advanced breast cancer of Egyptian patients receiving neoadjuvant chemotherapy.

PURPOSE: PARP-1 is a chromatin-associated enzyme that has a role in DNA repair and cell death. PARP-1 inhibitors are suggested therapy specifically for BRCA deficient breast carcinoma; however, their efficacy in sporadic breast cancer is under investigations. This study aimed to evaluate the PARP-1 in locally advanced breast cancer (LABC) cases to determine its predictive significance for outcome and response to neoadjuvant chemotherapy (NCT). MATERIALS AND METHODS: This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of nuclear PARP-1 (nPARP-1) and cytoplasmic PARP-1 (cPARP-1) was evaluated in pretreatment needle core biopsies (NCBs). Results were correlated with clinicopathologic features, overall survival (OS), disease-free survival (DFS), and response to NCT in postoperative specimens. RESULTS: High nPARP-1expression was observed in 64/84 (76%) of cases and was significantly associated with a lower lymph node stage (P=0.04). High cPARP-1 was observed in 40/84 (48%) of cases and it was significantly associated with lower lymph node stage (P=0.022) and lower tumor grade (P=0.050). High nPARP-1 expression was significantly associated with high cPARP-1 expression (P=0.005). Low cPARP-1 expression was associated with no response to chemotherapy in tumor site (P=0.021). According to the univariate survival analysis, high nPARP-1 and high cPARP-1 were significantly associated to longer OS (P=0.017 and P=0.019, respectively). High nPARP-1 but not cPARP-1 showed trend toward improved OS in multivariate Cox-regression analysis (P=0.053). CONCLUSION: PARP-1 immunohistochemical expression is a marker of good prognosis and is predictive of response to NCT in LABC.

Pleural mesothelioma: diagnostic problems and evaluation of prognostic factors.

BACKGROUND: Malignant pleural mesothelioma (MPM) in Egypt is mainly attributed to an environmental origin i.e exposure to asbestos, with a high incidence in women and young adults. Immunohistochemistry and ultrastructural features aid in the diagnosis. The p27Kip1 is a kinase inhibitor protein acting as a cell cycle regulator and a putative tumor suppressor gene playing a critical role in the pathogenesis of several human neoplasms. AIM: A clinicopathologic, immunohistochemical and ultrastructural study of mesothelioma in Egyptian patients, with identification of different prognostic factors. MATERIAL AND METHODS: Sixty-one cases of MPM were collected from the department of pathology at the NCI, Cairo. Cases were stained by monoclonal antibodies against CK5/6, calretinin, vimentin, CD15, CEA and p27. RESULTS: More than half (57.4%) of the patients were residents in endemic areas; 50.8% were of epithelioid type. CK5/6 was positive in 45 (73.8%) cases, 39 (63.9%) cases were positive for vimentin, 49 (80.3%) cases were positive for calretinin. One case showed a focal weak positive reaction to CD15. None of the cases stained for CEA. There was a statistically significant relation between p27 expression and the histopathologic type (p=0.02) between overall survival and age (p=0.01), histopathologic type (p=0.02) and stage (p=0.006). CONCLUSION: MPM is an increasing disaster in Egypt which is underestimated and neglected. A panel of immunohistochemical markers should be used for proper evaluation. p27 has proven to be a potential biologic prognostic marker for mesothelioma and more studies as regard its significance are recommended on a larger number.