{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:34:46Z","timestamp":1790094886473,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Neuroendocrine carcinoma, small cell type, of the uterine cervix (Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\u2010Cx) is a rare human papilloma virus (<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>) related tumour with limited therapeutic options. Merkel cell carcinoma, another virus\u2010associated neuroendocrine malignancy, has significant programmed death ligand 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1) expression rates. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression has been reported in other malignancies of the cervix. We aimed to determine the prevalence of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 in the context of mismatch repair protein (<jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">RB<\/jats:styled-content>1 expression status in Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\u2010Cx.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Ten cases of Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\u2010Cx were tested by immunohistochemistry for expression of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1, <jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>6, <jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">RB<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>20 and for <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> by <jats:italic>in\u2010situ<\/jats:italic> hybridisation (<jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression was scored quantitatively (H\u2010score) in tumour cells and lymphocytes (tumoral\/peritumoral). <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 positivity was seen in seven cases, focal in most (H\u2010score range 3\u2013140). Three of nine cases showed <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> deficiency. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression levels correlated with <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> expression status: all three <jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2\u2010deficient cases had a \u22655% <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 staining and an H\u2010score \u226510 (<jats:italic>P<\/jats:italic> = 0.01). <jats:styled-content style=\"fixed-case\">RB<\/jats:styled-content>1 was lost in four of nine cases, all <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 positive, but this correlation was not statistically significant. Seven of nine tumours were positive for <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content>; two of these had <jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2 loss. Of the two <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content> negative tumours, one had <jats:styled-content style=\"fixed-case\">MLS<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2 loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression, predominantly focal, is seen in 70% of Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\u2010Cx, while loss of <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> expression is seen in 33% of Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\u2010Cx in our cohort. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression in more than 10% of tumour cells is seen in a subset of tumours in association with loss of <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> expression. These patients may be amenable to immune checkpoint inhibitor therapy as a promising alternative for this aggressive disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13825","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T21:44:43Z","timestamp":1548279883000},"page":"997-1004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["<scp>PD<\/scp>\u2010L1, <scp>RB<\/scp>1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix"],"prefix":"10.1111","volume":"74","author":[{"given":"Sarah","family":"Morgan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Slodkowska","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada"},{"name":"Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-7291","authenticated-orcid":false,"given":"Carlos","family":"Parra\u2010Herran","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada"},{"name":"Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4042-8389","authenticated-orcid":false,"given":"Jelena","family":"Mirkovic","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada"},{"name":"Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2000.6118"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2017.11.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/mco.2013.193"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11086"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2001.6201"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdg333"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4081\/rt.2011.e6"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2018.02.009"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2016-0517"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0386"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S152232"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2151"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1277308"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000783"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.6326"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-017-0631-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.64"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.108"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40661-017-0038-9"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30364-3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2017.1394552"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.11.010"},{"key":"e_1_2_7_26_1","first-page":"10","article-title":"Surgically treated, early\u2010stage neuroendocrine small\u2010cell cervical carcinoma","volume":"71","author":"Sheets EE","year":"1988","journal-title":"Obstet. 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