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Published on: July 28, 2010
Molecular pathological subclassification of mucinous adenocarcinoma of the colorectum
Dong Li1, Shuho Semba, Ming Wu
1Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
The purpose of the present report was to examine the possibility of molecular pathological subtyping of mucinous adenocarcinomas (MAC) of the colorectum. Thirty-five formalin-fixed and paraffin-embedded MAC specimens of the colorectum were analyzed. Genetic alterations of p53 gene and microsatellite instability (MSI) as well as immunohistochemical analysis of mucin subtypes (human gastric mucin (HGM), anti-mucin monoclonal antibody recognizing gastric gland mucous cells-1, MUC2, CD10) and expression levels of human mutL homolog 1 (hMLH1), p53 and Ki-67 were performed. According to MSI and p53 status, these tumors were subclassified into three groups: mutator-type tumors with a high frequency of MSI (20%), suppressor/p53-type tumors with p53 mutation, p53 overexpression or loss of heterozygosity of D17S250 (an adjacent locus to p53; 40%) and the unclassified tumors (40%). The suppressor/p53-type tumors had a significant association with distal colon location (P = 0.019), venous invasion (P = 0.002), extent of lymph node metastasis (P = 0.007) and higher tumor stage (P = 0.018). In contrast, mutator-type tumors had frequent expression of HGM (P = 0.005) and prominent lymphocytic infiltration at the advancing front of the tumor (P = 0.005). These results indicate that MAC of the colorectum could be subclassified according to molecular pathological background, reflecting distinct clinicopathological and phenotypic characteristics.
Insights
Colorectal mucinous adenocarcinomas can be subtyped based on molecular pathology, specifically microsatellite instability (MSI) and p53 gene status. These molecular subtypes correlate with distinct clinicopathological features and tumor behavior.
Area of Science:
- Oncology
- Molecular Pathology
- Gastroenterology
Background:
- Mucinous adenocarcinomas (MAC) of the colorectum represent a distinct histological subtype.
- Understanding the molecular underpinnings of MAC is crucial for accurate prognostication and targeted therapy.
- Current classification primarily relies on morphology, potentially missing key molecular differences.
Purpose of the Study:
- To investigate the feasibility of molecular pathological subtyping for colorectal MAC.
- To identify distinct molecular subtypes based on genetic alterations and protein expression.
- To correlate these molecular subtypes with clinicopathological features and tumor behavior.
Main Methods:
- Analysis of 35 formalin-fixed, paraffin-embedded colorectal MAC specimens.
- Assessment of p53 gene alterations and microsatellite instability (MSI).
- Immunohistochemical analysis for mucin subtypes (HGM, MUC2, CD10) and expression of hMLH1, p53, and Ki-67.
Main Results:
- Three molecular subtypes were identified: mutator-type (20%), suppressor/p53-type (40%), and unclassified (40%).
- Suppressor/p53-type tumors showed associations with distal location, venous invasion, lymph node metastasis, and higher tumor stage.
- Mutator-type tumors frequently expressed human gastric mucin (HGM) and exhibited prominent lymphocytic infiltration.
Conclusions:
- Colorectal MAC can be effectively subtyped based on molecular pathological characteristics.
- These molecular subtypes exhibit distinct clinicopathological and phenotypic profiles.
- Molecular subtyping offers a promising approach for refining diagnosis and understanding the behavior of colorectal MAC.
