STK11 (LKB1) immunohistochemistry is a sensitive and specific marker for STK11 adnexal tumours.
LKB1
STK11
STK11 adnexal tumour
fallopian tube
female adnexal tumour of Wolffian origin
ovary
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
21 Aug 2024
21 Aug 2024
Historique:
revised:
03
08
2024
received:
24
05
2024
accepted:
06
08
2024
medline:
22
8
2024
pubmed:
22
8
2024
entrez:
22
8
2024
Statut:
aheadofprint
Résumé
ST11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz-Jeghers syndrome. It predominantly originates from the para-adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non-specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics. IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli-Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra-ovarian sex cord-stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo-ovarian high-grade serous carcinomas, five ovarian mesonephric-like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high-grade serous carcinoma with subclonal loss. STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : P50CA240243
Pays : United States
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
Bennett JA, Young RH, Howitt BE et al. A distinctive adnexal (usually paratubal) neoplasm often associated with Peutz‐Jeghers syndrome and characterized by STK11 alterations (STK11 adnexal tumor): a report of 22 cases. Am. J. Surg. Pathol. 2021; 45; 1061–1074.
Bennett JA, Oliva E. The complex and often confusing history, histology and histogenesis of mesonephric, STK11 adnexal tumour and mesonephric‐like neoplasms of the upper female genital tract (including broad ligament). Histopathology 2022; 81; 280–296.
Sharma AE, Slack JC, Parra‐Herran CE et al. STK11 adnexal tumor in an adolescent female: diagnostic pitfalls of a recently described entity. Pediatr. Dev. Pathol. 2023; 26; 486–493.
Mascaro N, Aboelnasr LS, Masood M, Yague E, Moran L, El‐Bahrawy M. Exploring the histogenesis of STK11 adnexal tumour using electron microscopy. Virchows Arch. 2024. https://doi.org/10.1007/s00428‐024‐03763‐2.
Calles A, Sholl LM, Rodig SJ et al. Immunohistochemical loss of LKB1 is a biomarker for more aggressive biology in KRAS‐mutant lung adenocarcinoma. Clin. Cancer Res. 2015; 21; 2851–2860.
Sahin F, Maitra A, Argani P et al. Loss of STK11/LKB1 expression in pancreatic and biliary neoplasms. Mod. Pathol. 2003; 16; 686–691.
Garcia EP, Minkovsky A, Jia Y et al. Validation of oncopanel: a targeted next‐generation sequencing assay for the detection of somatic variants in cancer. Arch. Pathol. Lab Med. 2017; 141; 751–758.
Stewart CJ, Alexiadis M, Crook ML, Fuller PJ. An immunohistochemical and molecular analysis of problematic and unclassified ovarian sex cord‐stromal tumors. Hum. Pathol. 2013; 44; 2774–2781.
Moore M, McCluggage WG. Uterine tumour resembling ovarian sex cord tumour: first report of a large series with follow‐up. Histopathology 2017; 71; 751–759.
Croce S, de Kock L, Boshari T et al. Uterine tumor resembling ovarian sex cord tumor (UTROSCT) commonly exhibits positivity with sex cord markers FOXL2 and SF‐1 but lacks FOXL2 and DICER1 mutations. Int. J. Gynecol. Pathol. 2016; 35; 301–308.
Hurrell DP, McCluggage WG. Uterine tumour resembling ovarian sex cord tumour is an immunohistochemically polyphenotypic neoplasm which exhibits coexpression of epithelial, myoid and sex cord markers. J. Clin. Pathol. 2007; 60; 1148–1154.
Goebel EA, Hernandez Bonilla S, Dong F et al. Uterine tumor resembling ovarian sex cord tumor (UTROSCT): a morphologic and molecular study of 26 cases confirms recurrent NCOA1‐3 rearrangement. Am. J. Surg. Pathol. 2020; 44; 30–42.
Laderian B, Mundi P, Fojo T, E. Bates S. Emerging therapeutic implications of STK11 mutation: case series. Oncologist 2020; 25; 733–737.
Alers S, Loffler AS, Wesselborg S, Stork B. Role of AMPK‐MTOR‐ULK1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol. Cell. Biol. 2012; 32; 2–11.
Faubert B, Vincent EE, Griss T et al. Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via hif‐1alpha. Proc. Natl. Acad. Sci. USA 2014; 111; 2554–2559.
Beggs AD, Latchford AR, Vasen HF et al. Peutz‐Jeghers syndrome: a systematic review and recommendations for management. Gut 2010; 59; 975–986.
Kuragaki C, Enomoto T, Ueno Y et al. Mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix. Lab. Investig. 2003; 83; 35–45.
Hodgson A, Howitt BE, Park KJ, Lindeman N, Nucci MR, Parra‐Herran C. Genomic characterization of HPV‐related and gastric‐type endocervical adenocarcinoma: correlation with subtype and clinical behavior. Int. J. Gynecol. Pathol. 2020; 39; 578–586.
Mackenzie R, Kommoss S, Winterhoff BJ et al. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping ras‐pathway activating mutations in borderline and cancerous neoplasms. BMC Cancer 2015; 15; 415.
Nishioka Y, Kobayashi K, Sagae S et al. Mutational analysis of STK11 gene in ovarian carcinomas. Jpn. J. Cancer Res. 1999; 90; 629–632.
Bennett JA, Ritterhouse LL, Furtado LV et al. Female adnexal tumors of probable wolffian origin: morphological, immunohistochemical, and molecular analysis of 15 cases. Mod. Pathol. 2020; 33; 734–747.
Mirkovic J, Dong F, Sholl LM et al. Targeted genomic profiling of female adnexal tumors of probable wolffian origin (FATWO). Int. J. Gynecol. Pathol. 2019; 38; 543–551.
Rajendran S, McCluggage WG. WT1 positive ovarian endometrioid tumors: observations from consult cases and strategies for distinguishing from serous neoplasms. Int. J. Gynecol. Pathol. 2022; 41; 191–202.
Mirkovic J, McFarland M, Garcia E et al. Targeted genomic profiling reveals recurrent KRAS mutations in mesonephric‐like adenocarcinomas of the female genital tract. Am. J. Surg. Pathol. 2018; 42; 227–233.
Kolin DL, Costigan DC, Dong F, Nucci MR, Howitt BE. A combined morphologic and molecular approach to retrospectively identify KRAS‐mutated mesonephric‐like adenocarcinomas of the endometrium. Am. J. Surg. Pathol. 2019; 43; 389–398.
da Silva EM, Fix DJ, Sebastiao APM et al. Mesonephric and mesonephric‐like carcinomas of the female genital tract: molecular characterization including cases with mixed histology and matched metastases. Mod. Pathol. 2021; 34; 1570–1587.
Shah R, McCluggage WG. Unclassifiable malignant extraovarian sex cord‐stromal tumors: report of 3 cases and review of extraovarian sex cord‐stromal tumors. Int. J. Gynecol. Pathol. 2017; 36; 438–446.
Karnezis AN, Wang Y, Keul J et al. DICER1 and FOXL2 mutation status correlates with clinicopathologic features in ovarian sertoli‐leydig cell tumors. Am. J. Surg. Pathol. 2019; 43; 628–638.
Connolly DC, Katabuchi H, Cliby WA, Cho KR. Somatic mutations in the STK11/LKB1 gene are uncommon in rare gynecological tumor types associated with peutz‐jegher's syndrome. Am. J. Pathol. 2000; 156; 339–345.
Tandon RT, Jimenez‐Cortez Y, Taub R, Borczuk AC. Immunohistochemistry in peritoneal mesothelioma: a single‐center experience of 244 cases. Arch. Pathol. Lab Med. 2018; 142; 236–242.
Park JY, Kim KW, Kwon HJ et al. Peritoneal mesotheliomas: clinicopathologic features, ct findings, and differential diagnosis. AJR Am. J. Roentgenol. 2008; 191; 814–825.
Kato S, Tomson BN, Buys TP, Elkin SK, Carter JL, Kurzrock R. Genomic landscape of malignant mesotheliomas. Mol. Cancer Ther. 2016; 15; 2498–2507.
Attanoos RL, Griffin A, Gibbs AR. The use of immunohistochemistry in distinguishing reactive from neoplastic mesothelium. A novel use for desmin and comparative evaluation with epithelial membrane antigen, p53, platelet‐derived growth factor‐receptor, p‐glycoprotein and bcl‐2. Histopathology 2003; 43; 231–238.