Accuracy of TNM staging in colorectal cancer: a review of current culprits, the modern role of morphology and stepping-stones for improvements in the molecular era

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. Survival is largely stage-dependant, guided by the tumor-node-metastases (TNM) system for TNM assessment. Histopathological evaluation, including assessment of lymph node status, is important for correct TNM staging. However, recent updates in the TNM system have resulted in controversy. A continued debate on definitions resulting in potential up- and downstaging of patients, which may obscure survival data, has led the investigators to investigate other or alternative staging tools. Consequently, additional prognostic factors have been searched for using the regular light microscopy. Among the factors evaluated by histopathology include the evaluation of tumor budding and stromal environment, angiogenesis, as well as involvement of the immune system (including the 'Immunoscore'). We review the current role of histopathology, controversies in TNM-staging and suggested alternatives to better predict outcome for CRC patients in the era of genomic medicine.

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

“…In a recent report, Lea et al described the limitations of the current TNM staging system in predicting the outcome of patients with CRC [20]. They suggested that the immune cell density in the stromal environment could be a better prognostic marker.…”

“…Galon et al introduced the ‘immunoscore (IS)’, a value based on the density of CD3 + and CD8 + lymphocytes in the tumor center (CT) and invasive margin (IM) [17–19]. Moreover, some authors have reported that the IS method is superior to the current tumor-node-metastases (TNM) staging system, especially in colon cancers [20, 21]. However, the evidence is limited to stages I–III of the disease [18, 22].…”

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3+ and CD8+ T-Cells in Colorectal Cancer

“…This becomes important as the current Tumour-Node-Metastasis (TNM) staging relies heavily on nodal status (with pN0 or pN+ for no or presence of node metastasis, respectively). Notably, TNM staging, although in widespread use, is imprecise with risk of both over-and undertreatment (13). Therefore, including information that may enhance staging precision beyond the lymph node status is needed.…”

Clinicopathological study of 9 cases of prostate cancer involving the rectal wall

“…However, a pathological confirmation using biopsy or FNA is necessary for a definitive diagnosis of prostate cancer [22, 23] because of the high incidence of both cancers in elderly patients. Differences in pathology between prostate and rectal cancers, including cytoarchitecture, glandular architecture, cellular pleomorphism, and mucosecretion patterns, can facilitate a correct diagnosis [24]. In rectal adenocarcinoma, tumor cells form irregular tubular structures, have multiple lumens, and have reduced stroma [25].…”