PubMed · 14249385
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C BLOCH, H M PECK. RADIOLOGICAL NOTES.. https://pubmed.ncbi.nlm.nih.gov/14249385/
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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.
CXC ligand 10 (CXCL10) and CXCL9 are chemoattractants for activated T cells and possess angiostatic activity. Both CXCL9 and CXCL10 have been considered as important components for the anti-tumour activities of interferon-gamma (IFNgamma) and interleukin-12 in animal models. In this article we show that the CXCL9 and CXCL10 genes in some types of human tumour cell lines are not inducible by IFNgamma and we describe experiments designed to explore the molecular mechanisms involved in this impaired induction. The human oral squamous carcinoma line Ca9-22 and the glioma line A172 failed to express CXCL9 and CXCL10 mRNAs in response to IFNgamma, whereas other carcinoma lines including HSC-2 did express these mRNAs. Production of these chemokine proteins was also impaired in Ca9-22 cells. The impaired expression was not due to any deficiency in the IFNgamma/signal transducer and activator of transcription 1 (STAT1)-dependent signalling pathway. Instead, analysis of nuclear factor kappaB (NF-kappaB) activity revealed that the constitutive low level of NF-kappaB activity, which is seen in cells that express these chemokines, was absent in Ca9-22 and A172 cells. Activation of NF-kappaB in Ca9-22 cells restored the expression of IFNgamma-stimulated CXCL9 and CXCL10 mRNAs. In contrast, inhibition of the constitutive NF-kappaB in HSC-2 cells by adenovirus-mediated gene transfer of a dominant-negative IkappaBalpha suppressed the IFNgamma-induced expression of the CXCL9 and CXCL10 mRNAs. These results indicate that constitutive NF-kappaB activity, which is often associated with tumour development, is required for the induced expression of CXCL9 and CXCL10 genes in human tumour cell lines in response to IFNgamma.
BACKGROUND: To examine the steroid hormone dependent growth mechanism of human endometrial hyperplasia and carcinoma, expression levels of steroid receptor cofactors, such as coactivators (steroid receptor coactivator 1 [SRC-1] and p300/cyclic AMP-response element-binding protein (p300/CBP]) and corepressors (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and thyroid-hormone receptors [SMRT]), were investigated. METHODS: The expression levels of cofactors were examined immunohistochemically using 20 samples of normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant endometria and were compared with the expression levels of estrogen receptor (ER), progesterone receptor (PR), and a proliferation marker, Ki-67. RESULTS: In samples of normal endometria, the expression of coactivators was observed diffusely in glandular cells in the proliferative phase, with a mean positivity index (PI) of 81.8 for SRC-1 and 91.3 for p300/CBP, whereas expression levels decreased in endometrial hyperplasia (PI: SRC-1, 58.9; p300/CBP, 83.8) and endometrial carcinoma (PI: SRC-1, 45.0; p300/CBP, 55.4). In endometrial hyperplasia, there was a significant correlation between the expression of ER and SRC-1 or p300/CBP. In contrast, there were no significant statistical or topologic correlations between the expression of coactivators and the expression of ER/PR in endometrial carcinoma. The expression of corepressors generally was limited, except for elevated expression of NCoR in endometrial hyperplasia (PI, 23.8). CONCLUSIONS: The current study showed that expression levels of the steroid receptor coactivators SRC-1 and p300/CBP were reduced in endometrial carcinoma compared with normal and hyperplastic endometrium. In addition, topologic coexpression of both coactivators and ER/PR was lost in endometrial carcinoma. Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR.