Raul S Gonzalez1, Won Jae Huh2, Justin M M Cates2, Kay Washington2, R Daniel Beauchamp3,4,5, Robert J Coffey4,6, Chanjuan Shi2. 1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA. 2. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. 3. Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 4. Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA. 5. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA. 6. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Abstract
AIMS: Colorectal carcinoma (CRC) with micropapillary (MP) features has only been described recently and is still being characterized. METHODS AND RESULTS: We reviewed the clinicopathological 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% (one 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 four 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: Micropapillary 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.
AIMS: Colorectal carcinoma (CRC) with micropapillary (MP) features has only been described recently and is still being characterized. METHODS AND RESULTS: We reviewed the clinicopathological 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% (one 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 four BRAFV600E 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: Micropapillary 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.
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