PubMed · 5098531
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M Ximenes Neto, P Atie. [Pelvic exenteration].. https://pubmed.ncbi.nlm.nih.gov/5098531/
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Amphicrine carcinomas of the stomach, defined by dual exocrine and neuroendocrine differentiation within the same neoplastic cell, are exceedingly rare. MUTYH-associated polyposis (MAP) is an autosomal recessive polyposis syndrome characterized by multiple colorectal adenomas and variable upper gastrointestinal involvement; however, amphicrine carcinomas have not been previously documented in this setting. We report a gastric amphicrine carcinoma arising in the background of extensive fundic gland polyposis in a patient with MAP. Endoscopy revealed a 3.5-cm flat elevated lesion in the gastric fundus amid extensive fundic gland polyposis. Histologically, the tumor consisted of a single population of cells exhibiting combined glandular and neuroendocrine differentiation without zonal or biphasic architecture, and many of these cells demonstrated true amphicrine morphology. Immunohistochemistry confirmed co-expression of cytokeratin and the neuroendocrine markers chromogranin A and synaptophysin in the same cell population. Germline targeted next-generation sequencing identified biallelic MUTYH variants in trans (c.733C>T, p.Arg245Cys [likely pathogenic]; c.842C>T, p.Ala281Val [variant of uncertain significance]), supporting a diagnosis of MAP. To our knowledge, this is the first reported case of a gastric amphicrine carcinoma in a MAP patient, expanding the spectrum of MAP-associated upper gastrointestinal neoplasia and underscoring the importance of vigilant endoscopic surveillance in hereditary polyposis syndromes.
Membrane-type metalloproteinase-I (MTI-MMP) is a transmembrane metalloproteinase, which activates pro-gelatinase A. There has been disagreement as to whether the cell types expressing MTI-MMP are cancer cells or stromal fibroblasts. Using human gastrointestinal carcinomas, the present study disclosed the tissue localization of MTI-MMP mRNA by in situ hybridization and ultrastructural localization of its protein by immunoelectron microscopy. In normal colon and stomach tissues, MTI-MMP mRNA and protein were negative or faintly positive both in epithelial cells and in stromal fibroblasts, except in the fundic gland of the stomach, which showed the positivity for MTI-MMP. In contrast, gastrointestinal cancer tissue showed over-expression of MTI-MMP mRNA and protein both in cancer cells and in stromal cells (fibroblasts). Stromal fibroblasts also expressed mRNA for gelatinase A and type-I procollagen. Double immunohistochemistry revealed that macrophages were also positive for MTI-MMP. Immunoelectron microscopy showed that MTI-MMP was localized along the plasma membrane of cancer cells and macrophages and in rough endoplasmic reticulum of fibroblasts. The present study reveals a dual over-expression pattern of MTI-MMP both in cancer cells and in stromal fibroblasts; the expression in cancer cells may be related to the invasive growth, whereas that in fibroblasts may be related to the tissue remodeling process caused by invasive growth of cancer cells.
BACKGROUND: The clinical value of DNA ploidy analysis in prostate carcinoma has been an issue for investigation for more than 2 decades. In general, diploid or pseudodiploid tumors are associated with a favorable prognosis and aneuploid tumors with an unfavorable prognosis, irrespective of type of treatment. Tumors with DNA values in the tetraploid region (around 4c) present a diagnostic problem. Such DNA distributions may clearly represent aneuploid tumors with an unfavorable prognosis. However, a 4c distribution may conversely represent a tetraploid tumor (possibly a polyploid variant of the diploid tumor) with a favorable prognosis. Previous data from our laboratory indicate the existence of such a tetraploid subgroup. The goal of the current study was to investigate the diagnostic problem of 4c tumors in greater detail. METHODS: Ploidy classification of cytologic smears by image cytometry was performed in a retrospective study of 334 patients with hormonally treated prostate carcinoma. Follow-up time was 30 years or until death. RESULTS: Three ploidy types were defined: near-diploid (D type), near-tetraploid (T type), and highly aneuploid (A type). Tumors with a modal value within the tetraploid region were found in 27% (92 cases) of the total material. Of these, 9% were defined as T type and 18% as A type. Overall, 37% of the tumors were classified as D type, 9% as T type, and 54% as A type. Of the A type tumors, one-third had modal DNA values in the tetraploid (4c) region. Multivariate analysis showed a statistically significant difference between A type tumors and D and T type, but not between D type and T type. Both D and T type tumors progressed slowly and killed the patients 5 to 30 years after diagnosis, whereas A type tumors progressed rapidly and killed the patients within 6 years of diagnosis. CONCLUSIONS: By image cytometry, prostate carcinoma can be divided into three ploidy types: D, T, and A type. Biologically, however, the tumors fall into only two groups: low grade malignant, pseudodiploid tumors of D or T type, and high grade malignant, highly aneuploid tumors of A type.