Assessment of clinicopathologic features of colorectal mucinous adenocarcinoma

doi:10.1016/S0002-9610(05)80969-9

The American Journal of Surgery

Volume 166, Issue 3, September 1993, Pages 257-261

https://doi.org/10.1016/S0002-9610(05)80969-9 Get rights and content

The purpose of this report is to analyze the clinicopathologic features of colorectal mucinous adenocarcinoma (MC), which is generally believed to have a poor prognosis, in an attempt to assess ways in which the surgical outcome can be improved.

Clinicopathologic features of 44 patients with MC (6.6%), from among 662 patients with primary colorectal cancers, were compared with those of 545 patients with nonmucinous (non-MC) adenocarcinoma. MC is more likely to invade the adjacent viscera (29% versus 10%, p<0.005) and show more extensive lymph node involvement beyond the pericolonic region (50% versus 26%, p<0.005) than non-MC. Based on these findings, a more aggressive attitude toward surgical intervention is recommended, including extensive lymph node dissection and the resection of adjacent organs that seem to be affected macroscopically, to improve the surgical outcome of this clinical entity.

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Citation Excerpt :
MCs account for 8%–10% of colon carcinomas and 33% of rectal cancers [10]. In principle, mucinous carcinoma is reported to show aggressive behavior and has been associated with poor prognosis in patients [11–13], and microsatellite instability (MSI) influences the overall survival of patients with MC. Patients with mucinous type CRC and high level of MSI (MSI-H) are reported to have better prognosis than patients with non-mucinous type CRC and MSI-H; however, patients with mucinous CRC and microsatellite stable (MSS) show worse prognosis compared to patients with non-mucinous CRC and MSS.
The genetic alterations (GAs) in two specific histological subtypes of colorectal cancer (CRC), signet ring cell colorectal carcinoma (SRC) and mucinous colorectal carcinoma (MC), are not well known. In the present study, we employed next-generation sequencing to perform genetic profiling of SRC and MC, and compared the spectrum of GAs with the alterations found in conventional type colorectal cancer (CON).
We selected 46 CRCs comprising 17 SRCs and mucinous carcinoma with signet ring cell component (SRCCs), 17 MCs, and 12 CONs with microsatellite stability or microsatellite instability-low. Deep sequencing was performed using a targeted cancer panel composed of 171 cancer-related genes. SMAD4 protein expression was evaluated by immunohistochemical staining.
We detected 108 mutations in 18 different genes. Overall, 2.34 GAs were detected per tumor (range, 0–14). The overall frequency of GA and alteration in targetable genes was less prevalent in SRC/SRCC compared to the frequency of alteration in MC/CON (p = 0.040 and p < 0.001, respectively). The GA profile of SRC/SRCC included TP53 (8/17, 47.1%), SMAD4 (5/17, 29.4%), KRAS (4/17.23.5%), APC (4/17.23.5%), PIK3CA, ATM, BRAF, and PIK3R1 (1/17, 5.9%, each). KRAS mutation was significantly less prevalent in SRC/SRCC compared to the number of KRAS mutations in MC (12/17, 70.6%) and CON (9/12, 75.0%) (p = 0.015 and 0.01, respectively). Compared to the 152 non-hypermutated CONs from TCGA database, SMAD4 alteration was predominant in SRC/SRCC (p = 0.045) with aberrant loss of SMAD4 expression (13/17, 76.5%) compared to the SMAD4 alterations in CON (5/15, 33.3%) (p = 0.031). Accordingly, KRAS (12/17, 70.6%), APC (6/17, 35.3%), SMAD4, TP53 (4/17, 23.5%, each), PIK3CA (3/17, 17.6%), AKT1, ATM, BRAF, EGFR, and EZH2 (1/17, 5.9%, each) were altered in MC. APC and TP53 mutations were less frequent in MC compared to those in TCGA-CON (p < 0.001 and 0.003, respectively) whereas KRAS mutation was prevalent (p = 0.041).
Alterations of known cancer associated genes and targetable genes in SRC/SRCC are infrequent. The profile of GAs in SRC/SRCC and MC differs from the GA profile of CON. Specifically, SMAD4 mutation and loss of SMAD4 expression is frequently found in SRC/SRCC. The genetic profiles revealed in the present study may aid in developing precision medicine for CRC treatment based on histological subtype.
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Citation Excerpt :
The term mucinous adenocarcinoma is reserved for high-grade tumours in which mucin-producing epithelial cells comprise more than 50% of the neoplastic cell population. Human mucinous adenocarcinomas are more likely to invade adjacent tissues, to metastasize to regional lymph nodes and to have a poorer prognosis compared with other types of alimentary adenocarcinoma (Yamamoto et al., 1993). CDX-2 is a nuclear transcription factor of the caudal homeobox family, which plays a key role in the regulation, proliferation and differentiation of intestinal epithelial cells during normal embryonic and post-natal development (Mallo et al., 1998; Silberg et al., 2000; Werling et al., 2003).
CDX-2 is used as a specific cell marker for human intestinal adenocarcinoma. In human studies, HER-3 overexpression predicts poor survival for patients with various cancers including gastric cancer. Gastrointestinal adenocarcinoma is less common in dogs than in man and the expression of immunological markers by the canine tumours has not yet been extensively studied. CDX-2 and HER-3 expression was determined in 18 canine gastrointestinal adenocarcinomas: 13 were of colorectal origin and five were of gastric origin. CDX-2 expression was predominantly observed in the nuclei of normal colonic epithelium and in neoplastic epithelium and neoplastic gastric epithelial cells that which had metastasized to the gastric lymph node. CDX-2 was expressed in 11 of 13 (84.6%) colorectal adenocarcinomas and in all five (100%) gastric adenocarcinomas. HER-3 was consistently expressed in the cytoplasm of neoplastic epithelial cells. HER-3 expression was detected in 12 of 13 (92.3%) colorectal and in all five (100%) gastric adenocarcinomas. CDX-2 and HER-3 may be useful markers for canine gastrointestinal adenocarcinoma.
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¹: From the Department of Surgery 1, National Defense Medical College,Namiki, Tokorozawa City, Saitama Prefecture, Japan.

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Assessment of clinicopathologic features of colorectal mucinous adenocarcinoma

Pathology

Clinicopathological studies of mucinous carcinoma of the large bowel

Jpn J Gastroenterologic Surg

Clinicopathological features of colorectal mucinous carcinoma

Jpn J Clin Surg

A study on mucinous colorectal carcinoma

Jpn J Gastroenterologic Surg

Mucinous carcinoma of the colon and rectum

Cancer

Peculiarities of mucinous colorectal carcinoma

Br J Surg

Mucoid carcinoma of the rectum

Cancer

Mucinous carcinomas of the colon and rectum and relation to polyps

Cancer