Epithelial-to-mesenchymal transition (EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer (CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical (IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapy- or radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMT-angiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.
Background. Plasmacytoid urothelial carcinoma is a rare and aggressive histologic variant of high-grade carcinoma of the urinary bladder. Few than 250 cases have been reported in the urinary bladder till January 2019. In this paper, a case series of unusual gastrointestinal carcinomas with plasmacytoid morphology was included. Only one similar case of the stomach was previously published and no such cases were found in colon. Methods. We present the complex immunoprofile, using a panel of 39 biomarkers, of the largest group of primary gastrointestinal carcinomas with plasmacytoid morphology reported in literature (one from upper rectum and six from stomach). Results. All of the seven cases showed lymph node metastases and only one survived over 25 weeks after surgical excision. The indicators of aggressivity were age (over 60), advanced stage (from IIIA to IV), E-cadherin negativity, and vimentin positivity. The immunoprofile indicated unfavorable prognosis for mesenchymal-type carcinomas (negativity for E-cadherin and positivity for vimentin, with membrane to nuclear translocation or negativity of β-catenin). The survivor showed an “epithelial-type adenocarcinoma with plasmacytoid dedifferentiation”, with membrane positivity for E-cadherin and β-catenin and vimentin negativity. All of the cases expressed c-MET and were negative for HER-2. Conclusions. Primary carcinoma with plasmacytoid morphology is a dedifferentiated variant of adenocarcinoma or poorly cohesive carcinomas. Vimentin positive dedifferentiated-poorly cohesive carcinomas should be considered as mesenchymal-type highly malignant carcinomas. This rare histologic variant of gastrointestinal cancer might respond to anti-c-MET tyrosine kinases.
Adrenocortical carcinoma is a rare tumor with high aggresivity that can associate systemic metastases.A 71-year-old man was hospitalized for gastric cancer. The abdominal computed tomography also revealed a tumor above the right kidney. Total gastrectomy and right adrenalectomy were performed. The encapsulated tumor of the adrenal gland weighed 560 grams and presented diffuse tumor architecture under microscope, with capsular, sinusoidal, and vascular invasion. The large tumor cells had a polygonal shape, with slight basophilic, eosinophilic, or vacuolated cytoplasm, pleomorphic nuclei, and a high mitotic rate. In the stomach, the protruded tumor was covered by normal mucosa; under microscope, the tumor cells were observed only in the submucosal layer. In primary adrenal tumor and gastric metastasis the tumor cells were marked by vimentin, inhibin, synaptophysin, neuron-specific enolase, and calretinin. Based on these criteria, the diagnosis of adrenocortical carcinoma (ACC) with gastric metastasis and no lymph node metastases was established. A synchronous 10 × 10-mm-sized gastrointestinal stromal tumor (GIST) of the stomach, without mitoses, was also identified.So far, as we know, this is the 15th case of ever reported synchronous/metachronous sporadic ACCs; the ACC-related gastric metastases either synchronous ACC and GIST, has not been reported in the literature previously.
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