DNA Mismatch Repair-deficient Rectal Cancer Is Frequently Associated With Lynch Syndrome and With Poor Response to Neoadjuvant Therapy.

Autor:	Farchoukh LF; Departments of Pathology., Celebrezze J; Surgery., Medich D; Surgery., Cunningham K; Surgery., Holder-Murray J; Surgery., Holtzman M; Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA., Lee K; Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA., Choudry H; Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA., Pai RK; Departments of Pathology.
Jazyk:	angličtina
Zdroj:	The American journal of surgical pathology [Am J Surg Pathol] 2022 Sep 01; Vol. 46 (9), pp. 1260-1268. Date of Electronic Publication: 2022 May 13.
DOI:	10.1097/PAS.0000000000001918
Abstrakt:	We evaluated 368 consecutively resected rectal cancers with neoadjuvant therapy for DNA mismatch repair (MMR) protein status, tumor response to neoadjuvant therapy, histopathologic features, and patient survival. Nine (2.4%) rectal cancers were mismatch repair-deficient (MMRD): 8 (89%) Lynch syndrome-associated tumors and 1 (11%) sporadic MLH1-deficient tumor. Of the 9 MMRD rectal cancers, 89% (8/9) had a tumor regression score 3 (poor response) compared with 23% (81/359) of MMR proficient rectal cancers ( P <0.001). Patients with MMRD rectal cancer less often had downstaging after neoadjuvant therapy compared with patients with MMR proficient rectal cancer (11% vs. 57%, P =0.007). In the multivariable logistic regression analysis, MMRD in rectal cancer was associated with a 25.11-fold increased risk of poor response to neoadjuvant therapy (tumor regression score 3) (95% confidence interval [CI]: 3.08-44.63, P =0.003). In the multivariable Cox regression analysis, the only variables significantly associated with disease-free survival were pathologic stage III disease (hazard ratio [HR]=2.46, 95% CI: 1.54-3.93, P <0.001), College of American Pathologists (CAP) tumor regression score 2 to 3 (HR=3.44, 95% CI: 1.76-6.73, P <0.001), and positive margins (HR=2.86, 95% CI: 1.56-5.25, P =0.001). In conclusion, we demonstrated that MMRD in rectal cancer is an independent predictor of poor response to neoadjuvant therapy and infrequently results in pathologic downstaging following neoadjuvant therapy. We also confirmed that MMRD in rectal cancer is strongly associated with a diagnosis of Lynch syndrome. Our results suggest that MMR status may help to provide a more patient-centered approach when selecting neoadjuvant treatment regimens and may help predict tumor response to neoadjuvant therapy. Competing Interests: Conflicts of Interest and Source of Funding: R.K.P. is a consultant for Alimentiv, and this relationship is unrelated to the content of this manuscript. For the remaining authors none were declared. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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