Predictors of phyllodes tumours on core biopsy specimens of fibroepithelial neoplasms.

AIMS: To establish histological and biological parameters that can predict phyllodes tumours on core biopsy specimens of indeterminate fibroepithelial neoplasms. METHODS AND RESULTS: Core biopsy specimens of fibroepithelial lesions diagnosed at the Department of Pathology, Singapore General Hospital from 2002 to 2007 were reviewed. Cases in which phyllodes tumour was favoured, or could not be ruled out, were evaluated for stromal cellularity/distribution, nuclear atypia and mitoses, stromal overgrowth, epithelial fronding, epithelial hyperplasia, configuration of lesional edge, presence of pseudoangiomatous stromal hyperplasia and of adipose tissue. Antibodies to Ki67, topoisomerase IIalpha, CD34, CD117 and Bcl-2 were applied to sections subjected to immunohistochemistry using the streptavidin-biotin method. Findings were correlated with subsequent excisions. Of 261 core biopsy specimens of fibroepithelial lesions, 98 (37%) comprised cases in which phyllodes tumour could not be excluded and 57 (58%) had subsequent open surgical excisions. Marked stromal hypercellularity (5/5; 100%) and nuclear atypia (1/1; 100%), stromal overgrowth (17/17; 100%), mitoses > or =2/10 high-power fields (18/18; 100%) and ill-defined lesional borders (16/16 phyllodes tumours; 100%) were features in core biopsy specimens that exclusively predicted phyllodes tumour on excision. Moderate stromal hypercellularity (20/27 phyllodes tumours; 74%), stromal overgrowth, moderate nuclear atypia (14/16 phyllodes tumours; 87%), pseudoangiomatous stromal hyperplasia (19/23 phyllodes tumours; 83%) significantly correlated with their subsequent excisions. Immunohistochemical markers Ki67 > or =5% and topoisomerase IIalpha> or =5%, and reduced or patchy CD34 on core biopsy specimens correlated significantly with a diagnosis of phyllodes. CONCLUSIONS: Stromal hypercellularity, combined with key histological features and immunohistochemical markers Ki67, topoisomerase IIalpha and CD34, reinforced by clinical findings, can predict phyllodes tumours on core biopsy specimens.

Hormone receptor and c-ERBB2 status in distant metastatic and locally recurrent breast cancer. Pathologic correlations and clinical significance.

Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers in the management of breast carcinoma. They are not always analyzed in distant metastatic and locally recurrent breast cancers. We compared immunohistochemical expression in a series of primary breast carcinomas with their distant metastases (n = 72) and local recurrences (n = 45) and analyzed the impact of any changes on survival. Discordance rates between primary and metastatic and between primary and locally recurrent lesions, respectively, were 18% (13/72) and 13% (6/45) for ER, 42% (30/72) and 33% (15/45) for PR, and 7% (5/72) and 2% (1/45) for c-ERBB2. There was statistically significant discordance between primary and metastatic PR status (P = .017; kappa = 0.201). Among locally recurrent tumors, 15 (33%) of 45 revealed discordance for PR (P = .006; kappa = 0.366). We observed a trend for shorter survival among women with ER- metastatic and locally recurrent tumors regardless of the primary tumor ER status. Our findings suggest a benefit for routine evaluation of ER, PR, and c-ERBB2 status in distant metastatic and locally recurrent breast cancer for therapeutic and prognostic purposes.

Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters.

Previous studies have suggested that breast cancer in young women has more aggressive biological features and poorer prognosis. However, the role of biological markers in these patients is not well understood. We aimed to learn more about this disease in a cohort of 125 young women from Singapore, Japan and Hong Kong, aged 35 years or less, with invasive breast cancer by evaluating the expression of vimentin and the basal cytokeratins CK14, CK5/6 and 34 beta E12. Both standard paraffin sections and tissue microarrays were used in the immunohistochemical evaluation of expression patterns of these four biological markers. CK5/6, CK14, vimentin and 34 beta E12, in increasing order of proportion, were detected in invasive carcinomas. Basal cytokeratins and vimentin showed significant inverse relationship with estrogen and progesterone receptor status while CK14 expression was found to be directly associated with c-erbB2 status. Basal cytokeratins and vimentin immunoreactivities were directly associated with CD117 and EGFR expression. Vimentin and 34 beta E12 immunopositivity correlated with tumor size, while vimentin was associated with higher histological grade. Our findings are in concert with reports that expression of basal cytokeratins and vimentin is correlated with adverse pathological parameters.

Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors.

Phyllodes tumors are fibroepithelial neoplasms typified by stromal proliferation. We have previously shown the role of pathologic parameters and the prognostic significance of p53 and CD117 protein expression in these tumors. In this study, we evaluated the expression of heparan sulfate, which has been implicated in many biological processes such as cell adhesion, embryogenesis, and tumorigenesis (including malignant transformation of mammary cells) in 232 breast phyllodes tumors. We used a monoclonal antibody, 10E4, to examine the localization of heparan sulfate in phyllodes tumors by immunohistochemistry. The immunoreactivity of both epithelial and stromal components was examined and analyzed with pathological parameters and other immunohistochemical markers, including p53, MIB1, bcl2, and CD117. Stromal 10E4 expression was significantly associated with tumor grade, stromal p53, and MIB1 expression in proliferating cells, suggesting that heparan sulfate may participate in malignant tumor growth.