Cyclin D1 expression predicts poor response to neoadjuvant chemotherapy and survival in late stage breast cancer patients

We evaluated the prognostic value of cyclin D1, epidermal growth factor receptor [EGFR] and MIB expression in Late Stage breast carcinoma, and their relationship with clinicopathologic response to neoadjuvant chemotherapy. We identified 45 patients who presented with locally advanced breast cancer [T2-T4], diagnosed with core needle biopsies, and treated with neoadjuvant chemotherapy, followed by conservative breast surgery [27/45,60%] with axillary lymph node dissection or modified radical mastectomy [18/45, 40%]. Complete pathologic response was defined as absence of invasive carcinoma at resection, while incomplete pathologic response was defined as having any invasive carcinoma. Cases were immunostained for cyclin D1, EGFR and MIB-1. Cyclin D1 ovcrexpression was found in 47% [21/45] of the cases and correlated with positive estrogen receptor [ER] expression [p < 0.01]. EGFR was positive in 16/45 [36%] of the cases which was expressed in the cytoplasm of the cancer cells, with occasional cell membrane staining. MIB-1 [>20%] was expressed in 15/45 [33%] of the cases. There were significant association between cyclin D1 overexpression and poor pathologic response [r=0.43, P=0.006], Cyclin D1 has significant adverse effect on overall survival and relapse-free survival [Log rank, p=0.05]. Overall, cyclin D1 overexpression was not associated with other clinicopathological features. EGFR was significantly expressed in ER and PR negative tumors [r=0.68 and 0.36, respectively]. Both EGFR and MIB-1 showed no significant correlation with pathologic response. Our findings indicate that cyclin D1 overexpression correlates with poor response to neoadjuvant chemotherapy and a worse survival in locally advanced breast cancer patients [T2-T4]

Peritumoral lymphatic microvessel density as a prognostic parameter in endometrial carcinoma

Lymphatic invasion and nodal metastasis play a major role in the spread and prognosis of endometrial adenocarcinoma [EC]. In this study, we investigated tumor lymph-angiogenesis, detected by D2-40, as a predictive marker for the risk of lymph node [LN] metastasis and its relation to other prognostic parameters in EC. Fifty-five cases of EC treated with total hysterectomy and pelvic LN dissection were reviewed. All cases were immunostained for D2-40. Positively stained microvessels [MV] were counted in densely lymphovascular foci [hotspots] at X400 field [0.17 mm[2]]. Lymphovascular invasion was detected in 20/55 patients by D2-40 and 14/55 by routine hematoxylin and eosin. Peritumoral lymphatic vessel [LV] count was significantly higher than intratumoral LV count [17+7 versus 5+4/0.17 mm[2], P< 0.01]. Peritumoral D2-40 lymphovascular count correlated significantly with FIGO grade [P <0.001], lymphovascular invasion [P=0.001] and lymph node [LN] metastases [P=0.005]. However it showed non-significant correlation with peritoneal wash positivity [P=0.830] and stage of the disease [P=0.341]. Lymphovascular invasion detected by D2-40 showed significant correlation with LN metastases [P<0.01]. Our study showed that assessing LVD with D2-40 in the endometrial carcinoma might be a valuable parameter for predicting patients having an increased risk of developing metastatic disease. In addition, D2-40 increases the frequency of detection of lymphatic invasion relative to routine hematoxylin and eosin stain

Distribution of basal / myoepithelial cells in well-differentiated adenocarcinoma and bronchioloalveolar proliferations of the lung

We investigated the staining pattern of commonly used basal cell/ myoepithelial markers such as p63 [a p53-homologous nuclear protein], basal cell-specific cytokeratin antibody [34 [3E12, K903] and smooth muscle myosin heavy chain [SMMHC] in benign and malignant bronchioloalveolar proliferations of the lung. Eighty-five lung lesions were included in the study, consisting of 35 bronchioloalveolar carcinoma, 30 well differentiated adenocarcinoma and 20 cases of benign lung lesions. In normal lung, p63, K903 and SMMHC decorated the basal cells of large and small airways and occasional cells of terminal bronchioles. In reactive processes, a distinctive staining pattern was present in 19/20 [95%] of the cases, characterized by staining of basal cells of the airways as well as bronchiolar-and squamous metaplastic epithelium for p63 and K903, while 12/20 [60%] stained with SMMHC. Respiratory ciliated cells, alveolar epithelial cells and nonepithelial cells were negative. In bronchioloalveolar carcinoma, a discontinuous peripheral rim of p63-immunoreactive cells was retained surrounding and intermingled with the malignant bronchioloalveolar proliferation in 31/35 [88.5%] cases, SMMHC in 28/35 [80%] and K903 in 20/35 [57%] cases. For adenocarcinoma, the majority of cases [28/30, 93%] were negative for p63 and K903; however, SMMHC showed artifactual staining in the desmoplastic stroma in 6/30 [20%] cases. Our results highlighted the differential expression of basal cell markers across various bronchioloalveolar lesions. The staining pattern of basal cells in bronchioloalveolar carcinoma support that these neoplasms may actually be carcinoma in-situ, which would explain their good prognosis and their tendency not to metastasize