Abstract: Objective To formulate a novel histological typing and grading-rated system for colorectal cancer (CRC) for
evaluating the biological behavior of CRC and prognosis. Methods According to the highly heterogeneous histological
features, WHO classification and histological differentiation criteria, and other biological behavior parameters of CRC, a novel
histological typing and grading-scale system for CRC was designed. The histological typing and corresponding grading-scale
of CRC was defined as the following: (1) No mucin-producing adenocarcinoma, including tubular adenocarcinoma, sieve-like
acne adenocarcinoma, medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc. (1-3 points); (2)
Mucin-producing adenocarcinoma, including mucinous adenocarcinoma and signet ring cell carcinoma (3-4 points); (3)
Squamous cell carcinoma (1-3 points); (4) Neuroendocrine tumors, including neuroendocrine tumors, neuroendocrine
carcinoma (1-4 points); (5) The special type of CRC, including clear cell carcinoma, spindle cell carcinoma, etc. (4-points); (6)
Undifferentiated carcinoma (5 points). The pathology report form was formated based on the major histological type with the
secondary histological type. The final total score of CRC was defined as the sum of the corresponding grading scores for
different histological types. The total score of a single-structure CRC was defined as the corresponding grading score
multiplied by 2. A total of 666 patients with advanced CRC were pathologically reviewed and analyzed to assess the
correlation of the histological typing and grading scores with TNM staging and lymph node metastasis. Results The results
showed a significant correlation of the histological grading-scale and TNM staging and lymph node metastasis (P<0.05). The
scores of CRC histological grading-scale increased synchronously with the TNM staging and lymph node metastasis rate.
Conclusion The novel histological grading system allows objective evaluation of the biological behaviors and prognosis of
CRC for determining individualized postoperative treatment. This system still needs further revision and updates based on
evidence from prospective, multi-centered, large-scale trials.