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

Abstract

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.

Analysis of tumor microenvironmental features to refine prognosis by T, N risk group in patients with stage III colon cancer (NCCTG N0147) (Alliance)

“…Micropapillary features in CRCs have also been linked to EMT, an increased frequency of p53 and KRAS mutations, lymph node metastasis, and a poor prognosis. 11,12 Nevertheless, our data in stage III tumors did not find an association of micropapillary features with KRAS or with DFS.…”

“…9 Micropapillary features may represent a continuum of tumor budding, 10 have been linked with EMT, and are associated with an increased frequency of mutations in KRAS and BRAF V600E and a poorer prognosis. 11,12 To date, however, studies of the association of these TME features with patient outcomes have typically been limited to patient case series of pooled tumor stages with variable treatment and follow-up.…”

Colon cancer with micropapillary carcinoma component: a clinopathologic study of 9 cases

“…It is possible that micropapillary carcinoma of the colon may resemble that of the bladder at the molecular genetic level. Gonzalez et al have recently reported that epithelial-mesenchymal transition is common in colon micropapillary carcinoma [23]. In contrast, micropapillary carcinoma does not seem to be involved in epithelial-mesenchymal transition, based on the results of this study.…”

Clinicopathological significance of heterogeneic ezrin expression in poorly differentiated clusters of colorectal cancers

“…The nuclear localization of β‐catenin, the lower expression of Ki‐67 and the cytosolic localization of E‐cadherin were observed in PDC . Frequent mutations in KRAS and BRAF were observed in CRC with MP features . Because our method of quantifying Ezrin heterogeneity in clusters can be applied to different kinds of proteins, IHC examination of other proteins in PDC will shed light on the mechanisms by which PDC progress and invade, and will help in the search for better markers for predicting prognosis.…”

“…MP patterns are characterized by small cell clusters without fibrovascular cores; the clusters are surrounded by empty lacunar spaces (Figure B). MP features in CRC showed a high likelihood of nodal involvement and of distant metastases …”