Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?

In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.

Differential expression of e-cadherin in primary breast cancer and corresponding lymph node metastases.

BACKGROUND/AIM: E-Cadherin is a marker with a controversial function. Its role is often interpreted in the context of the epithelial-mesenchymal transition. In ambiguous cases, it is used as a phenotypic marker of lobular subtype of breast carcinoma. It has been well-studied in primary cancer, but its expression after metastasis is not well-described. The aim of this study was to determine the evolution of E-cadherin expression in no special type (NST) primary breast carcinoma and to correlate this with that in distant, paired nodal metastases (LNM) and molecular classification. MATERIAL AND METHODS: We processed 88 invasive breast carcinomas of NST type and their paired LNM. The specimens were formalin-fixed and paraffin embedded. Sections were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), basal cytokeratin CK5, nuclear protein Ki67 and E-cadherin with a Leica Bond-Max autostainer. RESULTS: The results obtained were grouped into four molecular subtypes: Luminal A, luminal B, HER2-overexpressing, and triple-negative/basal-like. We found that the frequency of E-cadherin expression was higher (95.45%) in primary sites than in LNM (72.73%). E-Cadherin from primary breast cancer correlated positively only with E-cadherin in LNM (p≤0.003). A single positive correlation of E-cadherin with ER (p≤0.007) LNM was found. CONCLUSION: E-Cadherin expression is not stable during the metastatic process. Its expression in LNM is lower than in primary sites. E-Cadherin expression in primary sites positively correlates with E-cadherin from LNM.

Hormone receptors and HER2 expression in primary breast carcinoma and corresponding lymph node metastasis: do we need both?

BACKGROUND: Scattered studies report on controversial results concerning evaluation of primary breast tumors and their matched lymph node metastases. Aim. To investigate the molecular profile of primary breast tumors and corresponding lymph node metastases (LNM) based on estrogen receptor (ER), progesterone receptor (PR) and human epiderma growth factor receptor-2 (HER2 protein). MATERIALS AND METHODS: Sixty-six primary tumors and corresponding axillary lymph node metastases were evaluated by immunohistochemistry for ER, PR and HER2 protein. According to these markers, cases were stratified as Luminal A, B, HER2 subtypes and triple-negative. Results. Thirteen out of 66 cases (19.7%) exhibited different tumor cell phenotypes in nodal metastases compared to primary breast tumors. All cases with hybrid phenotype had metastases with a pure HER2 phenotype. The most frequent switching was observed from luminal A to luminal B phenotype. CONCLUSION: The high rate of discrepancy between primary tumor and nodal metastasis phenotype imposes the need for a comparative assessment of both primary tumor and nodal metastasis before any therapeutic decision, in order to avoid recurrence and to improve patient prognosis and overall survival.

Detection of early lymphangiogenesis by lymphatic microvascular density and endothelial proliferation status in preneoplastic and neoplastic lesions of the uterine cervix.

The characteristics of lymphangiogenesis in preneoplastic and neoplastic lesions of the uterine cervix are not well known and the role of this process in tumor progression and metastasis is not well understood. The aim of the present study was to characterize the morphology and distribution of lymphatic vessels and lymphatic proliferative status and to evaluate the value of lymphatic microvascular density (LMVD) in premalignant and malignant lesions of the uterine cervix. One hundred and twenty-eight paraffin-embedded cervical specimens were immunostained with D2-40 antibody specific for lymphatic endothelial cells. Colocalization of D2-40 and Ki67 for the proliferative characterization of lymphatic vessels was obtained by performing double immunostaining. A low density of lymphatic vessels was detected in normal cervix and squamous metaplasia. Intense and particular lymphangiogenic response was found in low and high grade squamous intraepithelial lesions and microinvasive carcinoma. Lymphatic proliferation occurred early in cervical lesions, being more active in premalignant lesions and microinvasive carcinomas than in invasive lesions. Our results suggest an early initiation of an active lymphangiogenesis in cervical lesions. These findings support the hypothesis that cervical preneoplastic lesions represent a critical point in the development of the lymphatic network vasculature. Early lymphangiogenesis could explain lymph node metastasis associated with cervical invasive carcinomas at preliminary diagnosis.

Characterization of endoglin and Ki-67 expression in endothelial cells from benign and malignant lesions of the uterine cervix.

Activation of endothelial cells is often associated with the cellular proliferation in vitro. CD105 is a more specific marker of activated endothelial cells from tumor vessels and Ki-67 is used to assess the proliferation status of both tumor and endothelial cells. The aim of the present study was to evaluate the status of endothelial cells using CD105 and Ki-67 immunohistochemistry in benign and malignant lesions of the uterine cervix. Double stain for CD105/Ki-67 in benign and malignant lesions of the uterine cervix showed that these two markers had divergent expression on endothelial cells from associated tumor blood vessels dependent on lesion type and proliferation status of tumor cells. Absence of CD105/Ki-67 coexpression in endothelial cells was correlated with histopathology of the uterine cervix lesions and tumor proliferative status. The present findings suggest that CD105 expression is an early event, specific for premalignant lesions of the uterine cervix, while endothelial proliferation assessed on Ki-67 combined with the lack of CD105 expression is often associated with invasive cervical carcinoma.

[Pulmonary epithelioid hemangioendothelioma--a case report]. / Hemangioendoteliom epitelioid pulmonar --prezentare de caz.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare soft tissue tumor of endothelial origin that occurs among young women and typically presents as bilateral multiple nodules, readily mistaken for carcinoma or, as in this case, Wegener's granulomatosis. This is a rare disease, with approximately 50 cases described in the literature. In the present report, we describe a case of PEH in a 39-yr-old woman. Immunohistochemically, the tumor cells were positive for CD34.