Connexin 43 is a potential prognostic biomarker for ewing sarcoma/primitive neuroectodermal tumor.

Connexins (Cxs) are building unit proteins of gap junctions (GJs) that are prognostic markers in carcinomas. To investigate the role of Cx in Ewing sarcoma (EWS)/primitive neuroectodermal tumor (PNET), we examined the expression of Cx43 and Cx26 in 36 EWS/PNETs and found (1) cytoplasmic Cx43 reactivity in 28/36 (78%) cases. (2) Cx43 score was significantly correlated with overall survival (P = .025). The average scores for patients alive and dead at 3 years are 46.08 and 96.98 (P = .004) at 5 years are 46.06 and 96.42 (P = .002). (3) Metastasis had a significant effect on the overall survival (P = .003). (4) Cytoplasmic Cx26 reactivity was detected in 2 of 36 (6%) patients who died with metastasis. Our results suggest a possible oncogenic and prognostic role for Cx43 and Cx26 in EWS/PNET. The lack of membranous immunoreactivity suggests that the effect of Cx in EWS/PNET is via a GJ function-independent mechanism.

Diagnostic value of differential expression of CK19, Galectin-3, HBME-1, ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an immunohistochemical tissue microarray analysis.

BACKGROUND: Several immunohistochemical markers have been used to aid in the diagnosis of follicular-derived lesions of the thyroid (FDLT). In this study we analyze the diagnostic efficacy of an immunopanel of antibodies to cytokeratin-19 (CK19), galectin-3 (GAL-3), HBME-1, anti-MAP kinase (ERK), ret-oncoprotein (RET), and p16 using a tissue microarray consisting of both benign and malignant FDLT. DESIGN: The study cohort consisted of 90 cases of FDLT (53 benign, 37 malignant) embedded in a microarray and immunostained with antibodies to CK19, Gal-3, HMBE-1, ERK, RET, and p16. Staining was scored as positive when >25% of the lesional cells showed positive immunostaining. RESULTS: HMBE-1 was expressed in 70% of malignant and 10% of benign FDLT (p value: <0.0001). CK19 and GAL-3 were positive in 70% and 73% of malignant lesions, respectively, and 34% of benign FDLT (p value 0.0005 and 0.0015, respectively). ERK was positive in 4% of the benign and 32% of the malignant cases (p value 0.0002). p16 was expressed in 2% and 46% of the benign and malignant lesions, respectively (p value 0.0001). RET positivity was identified in 15% of the benign lesions and 27% of the malignant cases (p value 0.0016). CONCLUSIONS: HBME-1, ERK, and p16 were more specific for malignancy, whereas CK19 and GAL-3 stained benign lesions with a higher frequency and were not specific for malignant FDLT. RET-oncoprotein showed poor sensitivity and specificity.

Undesirable cytokeratin immunoreactivity of native nonepithelial cells in sentinel lymph nodes from patients with breast carcinoma.

CONTEXT: Use of cytokeratin immunohistochemistry on histologically negative sentinel lymph nodes (SLNs) in patients with breast carcinoma has been shown to be efficient in detecting false-negative nodes. Several recent studies have shown that micrometastases detected by immunohistochemistry constitute an independent predictor of disease-free period and overall survival for breast cancer patients. It has been demonstrated that the fibroblastic type of reticulum cells in lymph nodes also express cytokeratin, and unawareness of such cytokeratin reactivity in SLNs could result in difficulty in the interpretation of the results of immunohistochemistry. OBJECTIVES: To study the incidence of undesirable cytokeratin reactivity in reticulum cells and other native nonepithelial cells of SLNs and to compare the immunoreactivity of 3 commonly used cytokeratin antibodies (AE1/AE3, pancytokeratin [pan-CK], and CAM5.2). DESIGN: Immunohistochemistry with pan-CK, AE1/AE3, and CAM5.2 antibodies was performed on paraffin sections of SLNs from patients with breast cancer. Correlation of undesirable cytokeratin reactivity with size and metastatic status of the SLNs was also analyzed. PATIENT MATERIAL: Paraffin sections of 84 SLNs from 38 consecutive patients with breast cancer in our tertiary-care, teaching hospital. RESULTS: Cytokeratin reactivity was found in reticulum cells and plasma cells in 29 (35%) and 9 (10%) of the 84 SLNs, respectively, with pan-CK and CAM5.2 but not with AE1/AE3 (P <.001). The presence of cytokeratin-positive reticulum cells did not correlate with the size and metastatic involvement of the SLNs. CONCLUSIONS: The incidence of undesirable keratin reactivity in SLNs from breast cancer patients could be limited by using an AE1/AE3 antibody cocktail. The AE1/AE3 antibody cocktail is a sensitive epithelial marker and appears to be more specific in recognizing epithelial cells in SLNs.

Intercellular adhesion molecule expression in ductal carcinoma of the breast: correlation of immunohistochemical staining with cytologic smear pattern.

Recent studies suggest that altered expression of intercellular adhesion molecules (ICAM) in ductal carcinoma of the breast is associated with a higher incidence of metastases and decreased patient survival. In addition, the presence of significant cellular dyscohesion in cytologic smear preparations has been found to correlate with the presence of regional and distant metastases in a subset of patients. In this study, we correlate the smear pattern in preparations taken directly from surgically excised breast tumors with their immunohistochemical staining pattern, using antibodies directed against a panel of ICAM. We found excellent correlation, as all three tumors with an extremely high degree of tumor cell cohesion showed strong staining with all ICAM antibodies in the vast majority (>/=90%) of tumor cells in corresponding tissue sections. In contrast, five tumors displaying a largely dyscohesive smear pattern demonstrated decreased staining (

Expression of prolactin and prolactin receptor in human breast carcinoma. Evidence for an autocrine/paracrine loop.

The neuroendocrine hormone prolactin is a growth factor required for the proliferation and terminal differentiation of the human breast. These effects are mediated by the prolactin receptor, a member of the growth factor receptor family. Three prolactin receptor isoforms (long, intermediate, and short) have been identified in the rat, which differ in the length of their intracytoplasmic domains. In humans, however, only the long prolactin receptor isoform had been identified previously. The expression of the human intermediate prolactin receptor is demonstrated and preliminary evidence for a human short isoform is presented. Heterogeneous expression of prolactin receptor, at the immunoblot and immunohistochemical levels was observed in breast carcinoma specimens. A statistically significant correlation between prolactin receptor and estrogen receptor expression was noted. An autocrine/paracrine role for prolactin within breast tissues was further examined by performing reverse transcription polymerase chain reaction on RNA isolated from cell lines and clinical specimens with prolactin-specific primers. A 585-bp product was observed and found to be identical to human prolactin. The synthesis of prolactin by breast epithelium was confirmed by in situ hybridization analysis of breast tissues and the detection of bio- and immunoreactive prolactin in breast cancer lines. These analyses indicate that the principal site for prolactin expression within the normal or malignant breast residues within the epithelium. These data indicate that prolactin may participate in an autocrine/paracrine stimulatory loop within breast tissues and suggest a role for this growth factor in the pathogenesis of breast cancer.