Histopathological atlas of desmoplastic reaction characterization in colorectal cancer.

Emergent scientific evidence indicates the central role of cancer-associated fibroblasts in determining whether the microenvironment of cancer works as friend or foe of the host; however, there is no unified histological evaluation framework of fibrotic stroma in colorectal cancers. Myxoid stroma and keloid-like collagen are site-specific histopathological features generated by cancer-associated fibroblasts, which appear exclusively in the tumor front during desmoplastic reaction. On the basis of these two stromal components, desmoplastic reaction is categorized into three patterns-immature, intermediate and mature-using hematoxylin and eosin staining. In January 2020, a prospective randomized clinical trial, JCOG1805, to elucidate the value of adjuvant chemotherapy in stage II colorectal cancer patients with pathological risk factors of recurrence was launched in Japan, in which intermediate/immature desmoplastic reaction is one of the four risk factors selected as inclusion criteria. This paper covers the diagnostic criteria for the desmoplastic reaction classification being used in the JCOG1805 study.

Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases.

BACKGROUND: Hepatic metastases from colorectal carcinoma frequently recur after resection and hepatic micrometastases most likely are important in the development of such recurrences. The objectives of the current study were to assess the feasibility of the immunohistochemical detection of hepatic micrometastases from colorectal carcinoma and to determine their clinical significance. METHODS: Fifty-three patients underwent curative hepatic resection for colorectal carcinoma metastases. Multiple tissue sections were cut from the advancing margin of the largest hepatic metastasis in each patient and were stained with an antibody against cytokeratin-20 to detect hepatic micrometastases, which were defined as discrete microscopic cancerous lesions surrounding the dominant metastasis. RESULTS: Normal hepatocytes and intrahepatic bile duct epithelia stained negative for cytokeratin-20 in all patients, whereas the largest hepatic tumors stained positive in 46 patients (86.8%). Among the 46 patients with hepatic tumors that were positive for cytokeratin-20, hepatic micrometastases were found immunohistochemically in 32 patients (69.6%). The presence of hepatic micrometastases was associated with a larger number of macroscopic hepatic metastases (P = 0.047) and patients with hepatic micrometastases were found to demonstrate a higher probability of intrahepatic recurrence (P = 0.003) compared with those patients without hepatic micrometastases. In addition, patients with hepatic micrometastases demonstrated a worse survival (10-year survival rate of 21.9%) compared with those patients without hepatic micrometastases (10-year survival rate of 64.3%) (P = 0.017). CONCLUSIONS: Immunohistochemical detection of hepatic micrometastases is feasible in patients with colorectal carcinoma liver metastases. Hepatic micrometastasis indicates widespread hepatic involvement and thus predicts an increased risk of intrahepatic recurrence after hepatic resection and a poorer patient prognosis.