Desmoplastic Pattern at the Tumor Front Defines Poor-prognosis Subtypes of Colorectal Cancer

Abstract

Although recent findings of cancer biology research indicate that prognostic power arises from genes expressed by stromal cells rather than epithelial cells, desmoplastic reaction (DR) has not been completely examined as a prognostic marker for colorectal cancer. A pathologic review of 821 stage II and III patients who underwent R0 resection for colorectal cancer at 4 independent institutions was conducted. DR was classified as mature, intermediate, or immature based on the existence of hyalinized keloid-like collagen and myxoid stroma at the extramural desmoplastic front. Totally, 325, 282, and 214 patients were classified as having mature, intermediate, and immature DR, respectively. DR significantly influenced the recurrence rate in the liver, lung, and peritoneum (P≤0.0001 to 0.01). Five-year relapse-free survival (RFS) rate was the highest in the mature group (85.7%), followed by the intermediate (77.3%) and immature (50.4%) groups. A significant adverse impact of immature stroma on RFS was observed in subset analyses of the 4 institutions. Multivariate analysis revealed that DR, along with T and N stages, is an independent prognostic factor. On the basis of Harrell's concordance index, the prognostic power of DR categorization (0.67) in stratifying RFS was greater than any other conventional prognostic factors, including TNM (0.64), N (0.62) and T stages (0.59), venous invasion (0.59), and tumor grade (0.54). Characterizing DR based on the histologic products of activated fibroblasts is valuable for evaluating prognostic outcomes. To our knowledge, this is the first study reporting a greater prognostic power of histology of the fibrotic stroma than that of tumor factors.

<p>Desmoplastic Reaction and Tumor Budding in Cervical Squamous Cell Carcinoma are Prognostic Factors for Distant Metastasis: A Retrospective Study</p>

“…20 Our results suggest that the prognostic power of DR categorization may be independent from the anatomical extent of the disease. 21,22 Notably, DR categorization was an independent factor for the prediction of survival in the current study. Few studies have focused on the morphological variations of the stroma pattern in CxSCC histopathology.…”

“…Previous studies have revealed that immature stroma are associated with higher activity of tumor budding. 11,22 The tumor dedifferentiation phenotypes at the invasive border are a morphologic feature of epithelialmesenchymal transition (EMT) 23,24 which is a vital molecular mechanism that allows tumor cells to obtain the ability to invade, survive, and metastasize. 23 Therefore, CAFs in tumors with immature stroma may regulate the tumor microenvironment through releasing various types of growth factors, cytokines and chemokines that enhanced EMT and subsequently drive metastasis.…”

Undervalued ubiquitous proteins

“…Furthermore, DnaK is upregulated in keloid tissues and scars [157] which can be basis for tumor development in various cancers [158][159][160]. In this regard, it may of importance to keep in mind the poor survival of subtypes of colorectal cancers with desmoplastic patterns [161] and the increase of desmoplasia in keloid tissues [162].…”

Histological assessment of stromal maturity as a prognostic factor in surgically treated gastric adenocarcinoma

“…Stromal tissue and stromal fibroblasts participate in tumour growth . In colorectal cancer, classifying tumours based on the type of desmoplastic stroma has prognostic significance . Less mature desmoplasia with myxoid stroma or thick, eosinophilic collagen fibres is associated with worse prognosis, compared to a desmoplastic reaction with mature, thin collagen fibres .…”

“…In colorectal cancer, classifying tumours based on the type of desmoplastic stroma has prognostic significance . Less mature desmoplasia with myxoid stroma or thick, eosinophilic collagen fibres is associated with worse prognosis, compared to a desmoplastic reaction with mature, thin collagen fibres . The analysis can be performed on routine haematoxylin and eosin (H&E) slides …”