Aims
Colorectal carcinoma (CRC) with micropapillary (MP) features has only been recently described and is still being characterized.

Methods and Results
We reviewed the clinicopathologic and molecular features of 42 CRC with MP features. Twenty-nine cases were also evaluated for immunohistochemical evidence of epithelial-mesenchymal transition (EMT). The extent of MP features within our cohort ranged from 5% (13 cases) to 100% (1 case). Twenty-seven cases featured prominent cribriforming with dirty necrosis in the non-MP component; nine displayed mucinous features. Twenty-four of 29 cases (83%) demonstrated evidence of EMT. Thirty-six cases (86%) showed advanced T-category (pT3 or pT4), 31 (74%) had lymph node metastases, and 23 (55%) had distant metastases. Median overall follow-up was 36 months. Seventeen patients (40%) died of disease, with median survival of 23 months. Mutations were seen in 17 of 31 tested cases (55%), including 11 KRAS mutations and 4 BRAF V600E mutations. Microsatellite instability testing was performed on 21 cases; all were microsatellite-stable. Compared to a cohort of 972 conventional CRC, MP CRC was more likely to present as Stage IV disease (P<0.001), but patients with MP CRC showed no significant differences in overall survival after adjusting for stage.

Conclusions
MP features in CRC portend a high likelihood of advanced local disease and distant metastases. MP CRC is often associated with a cribriform pattern elsewhere in the tumour and cystic nodal metastases with prominent necrosis. They also show frequent mutations in KRAS and BRAF. Immunohistochemical evidence of EMT is common in MP CRC.

This article is protected by copyright. All rights reserved.

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Micropapillary colorectal carcinoma: clinical, pathological and molecular properties, including evidence of epithelial-mesenchymal transition.

Invasive micropapillary carcinoma (IMPC) is a rare histological type of tumor, first described in invasive ductal breast cancer, than in malignancies in other organs such as lungs, urinary bladder, ovaries or salivary glands. Recent literature data shows that this histological lesion has also been found in cancers of the gastrointestinal system. The micropapillary components are clusters of neoplastic cells that closely adhere to each other and are located in distinct empty spaces. Moreover, clusters of neoplastic cells do not have a fibrous-vascular core. The IMPC cells show reverse polarity resulting in typical ‘’inside-out’’ structures that determines secretary properties, disturbs adhesion and conditions grade of malignancy in gastrointestinal (GI) tract. Invasive micropapillary carcinoma in this location is associated with metastases to local lymph nodes and lymphovascular invasion. IMPC can be a prognostic factor for patients with cancers of the stomach, pancreas and with colorectal cancer since it is related with disease-free and overall survival. The purpose of this review is to present the characterization of invasive micropapillary carcinoma in colon, rectum, stomach and others site of GI tract, and to determine the immunohistological indentification of IMPC in those localization.

Invasive micropapillary carcinoma: A distinct type of adenocarcinomas in the gastrointestinal tract

Background A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential pharmacological activities, particularly anticancer activities. Objective Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Methods Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by 1HNMR, 13C NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Results Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 13l selectively inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841 cells. Furthermore, compound 13l also selectively promoted intracellular ROS accumulation in HCT116 which was involved in 13l inhibition of cancer cell proliferation and induction of cell apoptosis. Finally, compound 13l also dose-dependently induced cancer cell apoptosis by regulating apoptotic and DNA damage related proteins expressions. Conclusion Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great promise as therapeutic agents for the treatment of human cancers.

Design, Synthesis, and Biological Evaluation of Novel Thiazolyl Substituted Bis-pyrazole Oxime Derivatives with Potent Antitumor Activities by Selectively Inducing Apoptosis and ROS in Cancer Cells.

Background
Invasive micropapillary carcinoma has been recognized as a rare disease entity with aggressive tumor behavior. However, few reports have described invasive micropapillary carcinoma in the gastrointestinal tract, particularly its involvement in gastric cancer.

https://link.springer.com/content/pdf/10.1007%2Fs10120-011-0094-5.pdf

Clinicopathological features of stomach cancer with invasive micropapillary component

Unresectable colorectal carcinomas (CRCs) as considered incurable even if the primary tumors and the metastatic ones can undergo resection are correlated with poor prognosis. We evaluated the association between micropapillary pattern at the invasive front and unresectable CRCs. Thirty-four out of 264 (12.9%) CRC patients with stages III and IV were unresectable cases. The patients with unresectable CRCs had significantly worse survival than those with resectable CRCs (P < 0.001). Micropapillary pattern was evident in 12 (4.5%) out of 264 cases. This pattern was observed in 6 of 34 (17.6%) unresectable CRCs and in 6 of 230 (2.6%) resectable cases (P = 0.002). Unresectable CRCs revealed more frequently deeper invasion (odds ratio (OR), 1.175; 95% confidence interval (CI), 1.113-1.241), lymph node metastasis (OR, 2.356; 95% CI, 1.132-4.905), and presence of micropapillary pattern at the invasive front (OR, 8.000; 95% CI, 2.415-26.504) as compared to resectable cases. By multivariable logistic regression analysis, only micropapillary pattern was shown to be an independent predictor of unresectable CRCs (OR, 9.451; 95% CI, 2.468-36.196; P < 0.001). In conclusion, micropapillary pattern at the invasive front is associated with unresectable CRCs, and detection of it could help identify unresectable CRC cases.

/pdf/micropapillary-pattern-at-the-invasive-front-and-its-rydfoqdwbo.pdf

Micropapillary Pattern at the Invasive Front and Its Association with Unresectable Colorectal Carcinomas

Invasive micropapillary carcinoma is associated with frequent lymph node metastases and adverse clinical outcome. It has been reported in breast, urinary bladder, lung and the parotid gland, but very rarely in the colon. We report a new case in a 63-year-old man involving the colon, and discuss the clinicopathologic features of this rare and particularly aggressive tumour.

Primary invasive micropapillary carcinoma of the colon: case report and review of the literature.

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Primary invasive micropapillary carcinoma of the colon: case report and review of the literature.