Bridging the Species Gap: Morphological and Molecular Comparison of Feline and Human Intestinal Carcinomas

Abstract

Limited availability of in vivo experimental models for invasive colorectal cancer (CRC) including metastasis and high tumor budding activity is a major problem in colorectal cancer research. In order to compare feline and human intestinal carcinomas, tumors of 49 cats were histologically subtyped, graded and further characterized according to the human WHO classification. Subsequently, feline tumors were compared to a cohort of 1004 human CRC cases. Feline intestinal tumors closely resembled the human phenotype on a histomorphological level. In both species, adenocarcinoma not otherwise specified (ANOS) was the most common WHO subtype. In cats, the second most common subtype of the colon (36.4%), serrated adenocarcinoma (SAC), was overrepresented compared to human CRC (8.7%). Mucinous adenocarcinoma (MAC) was the second most common subtype of the small intestine (12.5%). Intriguingly, feline carcinomas, particularly small intestinal, were generally of high tumor budding (Bd) status (Bd3), which is designated an independent prognostic key factor in human CRC. We also investigated the relevance of feline CTNNB1 exon 2 alterations by Sanger sequencing. In four cases of feline colonic malignancies (3 ANOS, 1 SAC), somatic missense mutations of feline CTNNB1 (p.D32G, p.D32N, p.G34R, and p.S37F) were detected, indicating that mutational alterations of the WNT/β-catenin signaling pathway potentially play an essential role in feline intestinal tumorigenesis comparable to humans and dogs. These results indicate that spontaneous intestinal tumors of cats constitute a useful but so far underutilized model for human CRC. Our study provides a solid foundation for advanced comparative oncology studies and emphasizes the need for further (molecular) characterization of feline intestinal carcinomas.

Pathological Findings in Gastrointestinal Neoplasms and Polyps in 860 Cats and a Pilot Study on miRNA Analyses

“…Intestinal carcinomas were classified as tubular (stomach) or acinar (intestine), papillary, undifferentiated (solid), signet-ring type, (adeno)squamous or mucinous [29,39] if most parts (approximately 75%) of the neoplastic tissue showed a morphology compatible with one pattern or the other.…”

“…Adenocarcinomas are the second most common intestinal neoplasm in cats [7]. Morphological and molecular genetic findings in feline intestinal carcinomas have been described in detail by Groll and colleagues [29]. Furthermore, mast cell tumours [30][31][32][33] and sarcomas [34][35][36][37][38] have been reported in the feline gastrointestinal tract.…”

Outcome and Prognostic Factors in Cats Undergoing Resection of Intestinal Adenocarcinomas: 58 Cases (2008–2020)

“…When slides were unavailable, the diagnosis was based on the initial histologic or cytologic reports and the pathologist was blinded to these reports. Tumors were histologically evaluated and classified according to the predominant histologic subtype, based on World Health Organization (WHO) criteria described for tumors of the colon in humans ( 12 ) as has been reported in previous feline intestinal tumor literature ( 13 , 14 ). Tumors were also categorized according to degree of glandular differentiation (well-differentiated or poorly-differentiated) ( 12 ).…”

An Editorial View on the Special Issue “Colorectal Cancers: From Present Problems to Future Solutions”

“…The article demonstrates how biomarkers, or biomarker panels, can be developed for single drugs, or drug combinations, within these CRC PDX models, or how, for example, alternative therapeutic strategies could be suggested in the individual case, depending on individual oncogenic pathway analysis. Finally, the original article by Katja Steiger and her group [ 13 ] introduces amazing similarities in morphology and molecular pathways between human and feline CRC, clearly inviting us to broaden our perspectives to other species of our planet, when attempting to understand, and conquer, human diseases such as CRC. I, personally, think that this is an article coming at the right time, given our actual global alert on the threats of climate change, the increasing extinction of whole species by humankind, and the several-fold overdone exploitation of our planet by the human species.…”