Dataset Information

Anal Canal Cancer : subclassification

ABSTRACT: Etiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCC) respond well to chemoradiotherapy, for undetermined reasons, a subgroup of patients experience a poor outcome. Despite cumulative efforts for discovering independent predictors for overall survival, both nodal status and tumor size are still the only reliable factors predicting patient outcome. In the present study, we correlated both proteomic signatures and clinicopathological features of neoplastic lesions arising from two distinct portions of the anal canal: the lower part (squamous zone) and the more proximal anal transitional zone. Although microdissected cancer cells appeared indistinguishable by morphology (squamous phenotype), unsupervised clustering analysis of the whole proteome significantly highlighted the heterogeneity that exists within anal canal tumors. More importantly, two region-specific subtypes of SCC were revealed. The expression profile (sensitivity/specificity) of several selected biomarkers (keratin filaments) further confirmed the subclassification of anal (pre)cancers based on their cellular origin. Less commonly detected compared to their counterparts located in the squamous mucosa, SCC originating in the transitional zone displayed more frequently a poor or basaloid differentiation and were significantly correlated with reduced disease-free and overall survivals. Taken together, we present for the first time direct evidence that anal canal SCC comprises two distinct entities with different cells of origin, proteomic signatures and survival rates. This study forms the basis for a novel dualistic classification of anal carcinoma with implications for management, outcome expectations and possibly therapeutic approaches.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Anal Canal

DISEASE(S): Anal Canal Cancer

SUBMITTER: Nicolas Smargiasso

LAB HEAD: Philippe Delvenne

PROVIDER: PXD004859 | Pride | 2016-12-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	150828-CTRL1-1-Anus-Remi-F01.raw	Raw
	150828-CTRL1-1-Anus-Remi-F02.raw	Raw
	150828-CTRL1-1-Anus-Remi-F03.raw	Raw
	150828-CTRL2-1-Anus-Remi-F01.raw	Raw
	150828-CTRL2-1-Anus-Remi-F02.raw	Raw

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Publications

Proteomic signatures reveal a dualistic and clinically relevant classification of anal canal carcinoma.

Herfs Michael M Longuespée Rémi R Quick Charles M CM Roncarati Patrick P Suarez-Carmona Meggy M Hubert Pascale P Lebeau Alizée A Bruyere Diane D Mazzucchelli Gabriel G Smargiasso Nicolas N Baiwir Dominique D Lai Keith K Dunn Andrew A Obregon Fabiola F Yang Eric J EJ Pauw Edwin De E Crum Christopher P CP Delvenne Philippe P

The Journal of pathology 20170127 4

Aetiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCCs) respond well to chemoradiotherapy, about 30% of patients experience a poor outcome, for undetermined reasons. Despite cumulative efforts for discovering independent predictors of overall survival, both nodal status and tumour size are still the only reliable factors predicting patient outcome. Recent efforts ha ...[more]

PMID: 27976366

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