PubMed · 104173
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1979-02-01. Case 38-1978.. https://doi.org/10.1056/nejm197902013000518
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The G12 subfamily of heterotrimeric G proteins, comprised of the alpha-subunits Galpha12 and Galpha13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elucidate specific roles of this subfamily in cell regulation, we sought to identify molecular targets of Galpha12. Here we show a specific interaction between the G12 subfamily and the cytoplasmic tails of several members of the cadherin family of cell-surface adhesion proteins. Galpha12 or Galpha13 binding causes dissociation of the transcriptional activator beta-catenin from cadherins. Furthermore, in cells lacking the adenomatous polyposis coli protein required for beta-catenin degradation, expression of mutationally activated Galpha12 or Galpha13 causes an increase in beta-catenin-mediated transcriptional activation. These findings provide a potential molecular mechanism for the previously reported cellular transforming ability of the G12 subfamily and reveal a link between heterotrimeric G proteins and cellular processes controlling growth and differentiation.
BACKGROUND: This study was designed to evaluate the significance of tumor angiogenesis and angiogenic factors such as hepatocyte growth factor (HGF) and c-Met in determining the prognoses of 93 patients with endometrial carcinoma. METHODS: By immunohistochemical staining, this retrospective study investigated tumor angiogenesis, HGF expression, and c-Met expression, using one tissue slide that was representative of the invasive edge of the tumor. To evaluate tumor angiogenesis, the microvessels within the primary endometrial carcinoma were highlighted by staining their endothelial cells immunohistochemically for von Willebrand factor (VWF). The microvessels were then counted in the most intense areas of neovascularization. HGF and c-Met were identified with specific antibodies. Tumor angiogenesis, HGF expression, and c-Met expression were correlated with both the prognostic variables for and the survival of endometrial carcinoma. RESULTS: A high microvessel count (> or = 110 in a 0.90 mm2 area) was significantly correlated with surgical Stage III and IV, histologic Grade 3, positive lymph node involvement, and shorter patient survival. Expression of c-Met was significantly correlated with surgical Stage III and IV, histologic Grade 3, and shorter survival. HGF expression was significantly correlated with surgical Stage III and IV by semiquantitative analysis. Multivariate analysis showed that surgical Stage III and IV, histologic Grade 3, the score for myometrial invasion > 1/2, and a high microvessel count were independent indicators of the prognoses of patients with endometrial carcinoma. CONCLUSIONS: Both tumor angiogenesis, measured by the microvessel count, and c-Met expression were significant prognostic indicators for patients with endometrial carcinoma.
BACKGROUND: Basal cell adenocarcinoma (BCAC) of the salivary gland is a rare tumor and recently described entity. Eleven cases of BCAC are presented here and compared with basal cell adenoma (BCA) through assessment of cell proliferative activity, apoptosis, and expression of p53, bcl-2, and epidermal growth factor receptor (EGFR) because these two tumors show close similarity in some cytologic and architectural characteristics. METHODS: Formalin fixed, paraffin embedded sections of 11 cases of BCAC and 9 cases of BCA, selected from the authors' files of 1851 primary tumors of the major salivary gland, were examined using immunostaining for Ki-67 (MIB-1), p53, bcl-2, and EGFR. In addition, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling. RESULTS: The incidence of BCAC was 0.6% among patients with major salivary gland tumors in the current series. Nine cases of BCAC arose in the parotid gland and two were of submandibular gland origin. Approximately 50% of the patients had recurrences, but no patient developed metastases or died of disease. Vascular involvement (75%), perineural invasion (36%), and necrosis (45%) were common features. Cell proliferative activity, including mitotic count, Ki-67 labeling index (LI), and apoptotic index were significantly higher in BCAC than BCA. More than four mitotic figures per ten high-power fields or a Ki-67 LI > 5% appeared to be limited to cases of BCAC. Considering those cases expressing p53 or EGFR in > 10% of tumor cells as positive, 6 of the 11 BCAC cases were positive for p53 and 3 were positive for EGFR. In contrast, all BCA cases were negative for p53 and EGFR. Although all cases of BCA were strongly positive for bcl-2 (> 50% of tumor cells), 3 of 11 cases of BCAC were completely negative. CONCLUSIONS: BCAC is a rare salivary gland tumor with a relatively high recurrence rate. Examination of cell proliferation, apoptosis, and expression of p53, bcl-2, and EGFR were found to be useful in distinguishing malignant basal cell tumors from their benign counterparts arising in the salivary gland.