TY - JOUR
T1 - Cribriform-Type adenocarcinoma of the colorectum
T2 - Comprehensive molecular analyses of a distinctive histologic subtype of colorectal cancer
AU - Yamada, Shun
AU - Osakabe, Mitsumasa
AU - Eizuka, Makoto
AU - Hashimoto, Mai
AU - Uesugi, Noriyuki
AU - Yanagawa, Naoki
AU - Otsuka, Koki
AU - Suzuki, Hiromu
AU - Matsumoto, Takayuki
AU - Sugai, Tamotsu
N1 - Publisher Copyright:
© 2022 The Author(s) 2022.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Colorectal adenocarcinoma (CRA) is characterized by marked heterogeneity and may be composed of an admixture of various histologic patterns, including well-formed gland and cribriform types. Although tumors displaying a prominent or predominant cribriform feature are frequently found in CRA, this type may contain specific histologic variants with a characteristic molecular alteration. We investigated the molecular features of 51 primary CRAs with a predominant cribriform histology using array-based analyses [somatic copy number alterations (SCNAs); mRNA expression]. Mutations (TP53, KRAS, PIK3CA and BRAF) and DNA methylation status were also analyzed. The crypt isolation method was used to obtain isolated tumor glands of each type separately. All patients were classified by their CRA histologic subtype into two groups: well-formed gland and cribriform. Next, we performed cluster analysis to stratify SCNA and mRNA expression patterns between the two subtypes. Two distinctive subgroups were stratified based on patterns of SCNA and mRNA expression and were correlated with each histologic subtype. The cribriform type was characterized by a high frequency of SCNA compared with that of the well-formed gland type and was closely associated with the expression of specific mRNAs. In addition, the frequency of KRAS mutation was significantly higher in the cribriform type than in the well-formed gland type. Finally, there was no difference in DNA methylation status between the two subtypes. Overall, these data suggest that the cribriform type provides important insights into colorectal carcinogenesis, suggesting specific potential histologic implications based on the molecular profile.
AB - Colorectal adenocarcinoma (CRA) is characterized by marked heterogeneity and may be composed of an admixture of various histologic patterns, including well-formed gland and cribriform types. Although tumors displaying a prominent or predominant cribriform feature are frequently found in CRA, this type may contain specific histologic variants with a characteristic molecular alteration. We investigated the molecular features of 51 primary CRAs with a predominant cribriform histology using array-based analyses [somatic copy number alterations (SCNAs); mRNA expression]. Mutations (TP53, KRAS, PIK3CA and BRAF) and DNA methylation status were also analyzed. The crypt isolation method was used to obtain isolated tumor glands of each type separately. All patients were classified by their CRA histologic subtype into two groups: well-formed gland and cribriform. Next, we performed cluster analysis to stratify SCNA and mRNA expression patterns between the two subtypes. Two distinctive subgroups were stratified based on patterns of SCNA and mRNA expression and were correlated with each histologic subtype. The cribriform type was characterized by a high frequency of SCNA compared with that of the well-formed gland type and was closely associated with the expression of specific mRNAs. In addition, the frequency of KRAS mutation was significantly higher in the cribriform type than in the well-formed gland type. Finally, there was no difference in DNA methylation status between the two subtypes. Overall, these data suggest that the cribriform type provides important insights into colorectal carcinogenesis, suggesting specific potential histologic implications based on the molecular profile.
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U2 - 10.1093/carcin/bgac029
DO - 10.1093/carcin/bgac029
M3 - Article
C2 - 35278309
AN - SCOPUS:85133102814
SN - 0143-3334
VL - 43
SP - 601
EP - 610
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -