TY - JOUR
T1 - Evaluating mismatch repair/microsatellite instability status using cytology effusion specimens to determine eligibility for immunotherapy
AU - Jacobi, Elizabeth M.
AU - Landon, Gene
AU - Broaddus, Russell R.
AU - Roy-Chowdhuri, Sinchita
N1 - Funding Information:
Supported by The University of Texas MD Anderson’s Department of Pathology Chairman Funds (EMJ) and NIH SPORE in Uterine Cancer NIH P50 CA09825 (RRB).
Publisher Copyright:
© 2021 College of American Pathologists. All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Context.-The approval of pembrolizumab for treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced cancers has led to increased requests for MSI and/or MMR immunoperoxidase (IPOX) testing. Diagnoses for patients with advanced-stage cancer are frequently made from cytology specimens. Objective.-To investigate the feasibility of using cell block (CB) preparations of effusions for MMR IPOX evaluation. Design.-Surgical pathology cases of colorectal and endometrial carcinomas with known MMR/MSI status and matched effusions with available CBs were identified. Cell block sections were evaluated for adequacy and stained with MMR IPOX (MSH2, MSH6, MLH1, and PMS2). The CBs were reviewed, the number of tumor cells quantified, and MMR IPOX was interpreted as retained, lost, suboptimal, or noncontributory. Results.-We identified 748 cases with MMR/MSI testing on surgical specimens having matched effusions. Of these, 131 cases (17.5%) had an available CB and 53 were deemed adequate for MMR IPOX staining. MMR IPOX results between effusion CBs and surgical pathology specimens were concordant in 45 of 53 (85%), inconclusive in 6 of 53 (11%), and discordant in 2 of 53 (4%) cases. Conclusions.-There was high concordance of MMR IPOX testing between cytologic and surgical specimens, with no false-positive and 2 false-negative CB results. Limited tumor cells, staining in cells indefinite as tumor, tumor staining heterogeneity, and lack of internal control staining were problematic in some cases. Our findings indicate that cytologic effusion specimens may be suitable substrates for MMR IPOX biomarker testing; however, inconclusive cases need to be interpreted with caution.
AB - Context.-The approval of pembrolizumab for treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced cancers has led to increased requests for MSI and/or MMR immunoperoxidase (IPOX) testing. Diagnoses for patients with advanced-stage cancer are frequently made from cytology specimens. Objective.-To investigate the feasibility of using cell block (CB) preparations of effusions for MMR IPOX evaluation. Design.-Surgical pathology cases of colorectal and endometrial carcinomas with known MMR/MSI status and matched effusions with available CBs were identified. Cell block sections were evaluated for adequacy and stained with MMR IPOX (MSH2, MSH6, MLH1, and PMS2). The CBs were reviewed, the number of tumor cells quantified, and MMR IPOX was interpreted as retained, lost, suboptimal, or noncontributory. Results.-We identified 748 cases with MMR/MSI testing on surgical specimens having matched effusions. Of these, 131 cases (17.5%) had an available CB and 53 were deemed adequate for MMR IPOX staining. MMR IPOX results between effusion CBs and surgical pathology specimens were concordant in 45 of 53 (85%), inconclusive in 6 of 53 (11%), and discordant in 2 of 53 (4%) cases. Conclusions.-There was high concordance of MMR IPOX testing between cytologic and surgical specimens, with no false-positive and 2 false-negative CB results. Limited tumor cells, staining in cells indefinite as tumor, tumor staining heterogeneity, and lack of internal control staining were problematic in some cases. Our findings indicate that cytologic effusion specimens may be suitable substrates for MMR IPOX biomarker testing; however, inconclusive cases need to be interpreted with caution.
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U2 - 10.5858/arpa.2019-0398-OA
DO - 10.5858/arpa.2019-0398-OA
M3 - Article
C2 - 33367660
AN - SCOPUS:85085762096
VL - 145
SP - 46
EP - 54
JO - Archives of Pathology and Laboratory Medicine
JF - Archives of Pathology and Laboratory Medicine
SN - 0003-9985
IS - 1
ER -