Clinicopathological and molecular features of hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas.

Abstract

AIMS:

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder caused by germline mutations in fumarate hydratase (FH). Affected families have an increased risk of renal cell carcinoma (RCC). HLRCC-associated RCC (HLRCC-RCC) is highly aggressive. Clinicopathological information of genetically diagnosed patients with HLRCC-RCC contributes to the establishment of effective therapies.

METHODS:

Ten Japanese patients with HLRCC-RCC were enrolled in the study. Genetic testing for FH was carried out. Somatic mutations in FH and immunohistochemical analyses of FH and B7 family ligands (PD-L1 and B7-H3) were investigated in 13 tumours. Copy number variations were evaluated in two tumours.

RESULTS:

All patients had FH germline mutations. Regarding histology, most tumours had type 2 papillary architecture or tubulocystic pattern or both. All tumours were FH deficient by immunohistochemistry. Ten tumours were positive for PD-L1, and 12 tumours were positive for B7-H3. Somatic mutation analysis demonstrated loss of heterozygosity of FH in 10 tumours. Copy number variation analysis revealed uniparental disomy between 1q24.2 and 1q44 encompassing FH; gain of chromosome 2 p was also common. All patients had either metastases or residual tumours. Three patients died of HLRCC-RCC and one of colon cancer, whereas the other six are currently alive, including two without recurrence.

CONCLUSIONS:

HLRCC-RCCs appear to have unique molecular profiles, including PD-L1 expression. One patient had complete response to immunotherapy, which may be an option for HLRCC-RCC.

• Authors: Mitsuko Furuya, Yasuhiro Iribe, Yoji Nagashima, Naotomo Kambe, Chisato Ohe, Hidefumi Kinoshita, Chika Sato, Takeshi Kishida, Yoichiro Okubo, Kazuyuki Numakura, Hiroshi Nanjo, Noboru Nakaigawa, Kazuhide Makiyama, Hisashi Hasumi, Hiromichi Iwashita, Junichi Ohta, Hiroshi Kitamura, Takahiko Nakajima, Takahiro Yoshida, Masahiro Nakagawa, Reiko Tanaka, Masahiro Yao
• Journal: Journal of clinical pathology (J Clin Pathol) Vol. 73 Issue 12 Pg. 819-825 (Dec 2020) ISSN: 1472-4146 [Electronic] England
• PMID: 32376712 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Fumarate Hydratase

Topics

• Adult
• Asian People
• DNA Copy Number Variations
• Female
• Fumarate Hydratase (genetics)
• Germ-Line Mutation
• Humans
• Leiomyomatosis (genetics, pathology)
• Male
• Middle Aged
• Neoplastic Syndromes, Hereditary (genetics, pathology)
• Skin Neoplasms (genetics, pathology)
• Uterine Neoplasms (genetics, pathology)