The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

Abstract

BACKGROUND: The proportion of epithelial and stromal cells in tumours is thought to have an important role in the progression of epithelial malignancy. We aimed to determine whether the relative proportion of tumour (PoT) was related to survival in colorectal cancer. METHODS: The PoT at the luminal surface was measured by point counting using virtual tissue sections in a series of 145 colorectal cancer cases. The relationship of PoT to clinicopathological parameters including cancer-specific survival was analysed. Modified receiver operating characteristic curves were used to determine the optimum cut off points to dichotomise the data for survival analyses. RESULTS: Tumours with PoT-low (p47%) were associated with significantly lower cancer-specific survival when compared to PoT-high (hazard ratio (HR) ¼ 2.087, 95% CI ¼ 1.088 -4.003, P ¼ 0.024). On sub-analysis, the prognostic effect remained significant in colonic tumours (HR ¼ 2.474, 95% CI ¼ 1.132 -5.408, P ¼ 0.019) and tumour, node, metastasis stage III disease (HR ¼ 3.480, 95% CI ¼ 0.325 -9.136, P ¼ 0.007). Multivariate Cox regression analysis demonstrated that PoT was an independent prognostic marker when adjusted for age, T stage, N stage and extramural vascular invasion (P ¼ 0.017). CONCLUSION: This study suggests that a low proportion of tumour cells in colorectal cancer is related to poor cancer-specific survival. A relatively quick, inexpensive and well-established method such as point counting on diagnostic tissue sections could be used to identify a subset of patients who may benefit from adjuvant therapy.

Tumor–stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

“…These observations corroborate previous findings [4,[6][7][8]10], and thus persist after neoadjuvant chemotherapy.…”

“…A low TSR in the surgically resected primary tumors was detected in 47% of the patients, a ratio comparable to the latest studies in the literature [4,5] although the initial studies generally indicated a lower frequency (24-29%) of 'low TSR' [6][7][8][9][10]. A possible influence of neoadjuvant chemotherapy on tumor tissue composition may explain, at least partly, this difference.…”

“…Most studies regarding the technical aspects of TSR scoring provide kappa-values pointing to at least moderate, but mostly substantial and even optimal reproducibility. The current literature unanimously points toward TSR as a prognostic marker in patients operated for colon cancer [4][5][6][7][8][9][10], although results from larger population based cohorts are still awaited. A high amount of stroma (low TSR) is related to a poor prognosis and may also influence the delivery of chemotherapeutics to the cancer cells.…”

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

“…Nevertheless, we think that it is crucial to investigate all these parameters further (individually or in combination) to assess mCRC patient prognosis: When implementing all these parameters in multivariate analysis for the entire cohort with all clinical standards, such as age, sex, tumor localization, and CEA, the study data revealed that ccfDNA parameters, such as total ccfDNA concentration (P ¼ 0.034; HR, 1.73; 95% CI, 1.04-2.89), as well as BRAF-mutant status (P ¼ 0.002; HR, 7.33; 95% CI, 3.13-25.4), are strong independent prognostic factors. Quantitative analysis of ccfDNA, especially the mA%, preferentially relies on tumor biology, in particular to the proportion and/ or activity of the tumor microenvironment which appears as a significant factor since a low proportion of malignant cells in colorectal cancer is related to poor cancer-specific survival (37). We previously reported the very high variation in mutation load (more than 2,000-fold) among the mCRC patients (35), an observation later confirmed by Bettegowda and colleagues (6).…”

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

“…Such biomarkers could be derived from imaging such as tumour regression grade (TRG) or response of EMVI [53,54]. Alternatively they could be pathological, such as changes in TRG or in tumour cell density (TCD) [55,56], or molecular, such as stratifiers of response to chemotherapy and radiotherapy.…”