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Prognostic Value of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma

Yonemura, Keisuke MD; Kajiwara, Yoshiki MD, PhD; Ao, Tadakazu MD; Mochizuki, Satsuki PhD; Shinto, Eiji MD, PhD; Okamoto, Koichi MD, PhD; Hase, Kazuo MD, PhD; Ueno, Hideki MD, PhD

The American Journal of Surgical Pathology: October 2019 - Volume 43 - Issue 10 - p 1341–1348
doi: 10.1097/PAS.0000000000001329
Original Articles

Colorectal liver metastasis (CRLM) is the most common pattern of metastases or recurrence in colorectal carcinoma; however, no robust pathologic prognostic factors have been identified. This study aimed to verify the prognostic value of poorly differentiated clusters (PDC) in liver metastatic lesions and to clarify the correlation between PDC in liver metastatic lesions (PDCliver) and the primary tumor histology. Consecutive patients who underwent resection for CRLM were pathologically reviewed. PDC was defined as cancer clusters comprising ≥5 cancer cells and lacking glandular formation and was quantifiably graded as G1 (<5 clusters), G2 (5 to 9 clusters), and G3 (≥10 clusters) based on the highest number of clusters observed under ×20 magnification. The cohort comprised 204 patients. PDCliver was classified as G1, G2, and G3 for 68, 69, and 67 patients, respectively, and it was significantly associated with PDC grade in the primary tumor (P<0.001). Among the potential prognostic factors, tumor budding in the primary tumor, PDC in the primary tumor, the number of liver metastases, extrahepatic metastasis, and PDCliver significantly influenced overall survival (OS) after CRLM resection. According to the PDCliver grade, the 5-year OS rates were 68.9%, 48.3%, and 39.5% for G1, G2, and G3 (P<0.001), respectively. Multivariate analysis for OS showed that PDCliver grade, tumor budding in the primary tumor, the number of liver metastasis and extrahepatic metastasis were independent prognostic factors. In conclusion, there is a correlation in the PDC grade between the primary tumor and liver metastatic lesion, and PDCliver grade could be a promising new prognostic factor after CRLM resection.

Department of Surgery, National Defense Medical College, Saitama, Japan

Conflicts of Interest and Source of Funding: The authors disclose that they have no significant relationships with or financial interest in any commercial companies related to this article.

Correspondence: Yoshiki Kajiwara, MD, PhD, Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan (e-mail:

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