title: Early signet ring cell carcinoma arising from colonic adenoma: the molecular profiling supports the adenoma-carcinoma sequence.
abstract: Among colorectal cancers, the prevalence of signet ring cell carcinoma (SRCC) is lower than 1%; to date, only 6 cases of early SRCCs arising in colonic adenoma have been reported. In spite of the well-established understanding of the phenotypic and genetic changes occurring in conventional colonic carcinogenesis, the molecular landscape of colon SRCC is still far to be elucidated. We describe the histologic and immunohistochemical phenotype and the molecular profile of a case of intramucosal SRCC developed within a 4.5-cm large sigmoid adenoma. The DNA sequencing of the 2 microdissected neoplastic components (adenomatous and SRCC) showed the same G12V KRAS mutation. Interestingly, although the adenomatous epithelium showed unequivocal p53 overexpression, no signet ring cancer cells featured p53 nuclear immunostain. This molecular pattern supports the unique histogenesis of the 2 coexisting neoplastic oncotypes, also suggesting that the signet ring cell component is derived from the molecular de-differentiation (p53 loss) of the preexisting adenomatous lesion.
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bellan
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cappellesso
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Lo Mele
authors.affiliation: Gastroenterology Unit, S. Antonio Hospital, 35127, Padua, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Peraro
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Balsamo
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Lanza
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy. Electronic address: matteo.fassan@unipd.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Medicine, Anatomic Pathology, University of Padua, 35121 Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D054337:Cell Dedifferentiation; D003082:Colectomy; D003110:Colonic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D004252:DNA Mutational Analysis; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Colorectal adenocarcinoma; KRAS; Molecular profiling; Preneoplastic lesions; Signet ring cell carcinoma