Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets
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Background: Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms Methods: We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets. Results: We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063). Conclusions: Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.
Abstract
Background: Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms Methods: We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets. Results: We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063). Conclusions: Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.
참고문헌 (42)
- Padala SA, "Epidemiology of renal cell carcinoma", World J Oncol, 11, pp.79~87 (2020)
- Sung WW, "Favorable mortality-to-incidence ratios of kidney cancer are associated with advanced health care systems", BMC Cancer, 18, pp.792~ (2018)
- Bai X, "The global, regional, and national burden of kidney cancer and attributable risk factor analysis from 1990 to 2017", Exp Hematol Oncol, 9, pp.27~ (2020)
- "SEER training modules, module name" (2023)[URL]
- Dudani S, "Evaluation of clear cell, papillary, and chromophobe renal cell carcinoma metastasis sites and association with survival", JAMA Netw Open, 4, pp.e2021869~ (2021)
- WHO Classification of Tumours Editorial Board, "Urinary and male genital tumours. WHO classification of tumours series, 5th ed., Vol. 8" (2022), International Agency for Research on Cancer
- Courthod G, "Papillary renal cell carcinoma : a review of the current therapeutic landscape", Crit Rev Oncol Hematol, 96, pp.100~112 (2015)
- Pitra T, "Chromosomal numerical aberration pattern in papillary renal cell carcinoma : review article", Ann Diagn Pathol, 40, pp.189~199 (2019)
- Cancer Genome Atlas Research Network, "Comprehensive molecular characterization of papillary renal-cell carcinoma", N Engl J Med, 374, pp.135~145 (2016)
- Furge KA, "Detection of DNA copy number changes and oncogenic signaling abnormalities from gene expression data reveals MYC activation in high-grade papillary renal cell carcinoma", Cancer Res, 67, pp.3171~3176 (2007)
- Ooi A, "CUL3 and NRF2 mutations confer an NRF2 activation phenotype in a sporadic form of papillary renal cell carcinoma", Cancer Res, 73, pp.2044~2051 (2013)
- Moch H, "WHO classification of tumours. 4th ed. Vol. 8. WHO classification of tumours of the urinary system and male genital organs" (2016), World Health Organization
- Chevarie-Davis M, "The morphologic and immunohistochemical spectrum of papillary renal cell carcinoma : study including 132 cases with pure type 1 and type 2morphology as well as tumors with overlapping features", Am J Surg Pathol, 38, pp.887~894 (2014)
- Chen X, "Mutant p53 in cancer : from molecular mechanism to therapeutic modulation", Cell Death Dis, 13, pp.974~ (2022)
- Al Ahmad A, "Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in both anabolic glucose synthesis and oxidative phosphorylation", Cancers (Basel), 11, pp.1298~ (2019)
- Yang H, "STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade", J Clin Invest, 129, pp.4350~4364 (2019)
- Schmidt L, "Novel mutations of the MET proto-oncogene in papillary renal carcinomas", Oncogene, 18, pp.2343~2350 (1999)
- Durinck S, "Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes", Nat Genet, 47, pp.13~21 (2015)
- Schmidt L, "Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas", Nat Genet, 16, pp.68~73 (1997)
- Zhang Y, "Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities", Mol Cancer, 17, pp.45~ (2018)
- Sierra JR, "c-MET as a potential therapeutic target and biomarker in cancer", Ther Adv Med Oncol, 3(1 Suppl), pp.S21~S35 (2011)
- Puccini A, "Safety and tolerability of c-MET inhibitors in cancer", Drug Saf, 42, pp.211~233 (2019)
- Choueiri TK, "Efficacy of savolitinib vs sunitinib in patients with MET-driven papillary renal cell carcinoma : the SAVOIR phase 3 randomized clinical trial", JAMA Oncol, 6, pp.1247~1255 (2020)
- Rhoades Smith KE, "A review of papillary renal cell carcinoma and MET inhibitors", Kidney Cancer, 3, pp.151~161 (2019)
- Foulkes WD, "The CDKN2A(p16)gene and human cancer", Mol Med, 3, pp.5~20 (1997)
- Zhao R, "Implications of genetic and epigenetic alterations of CDKN2A(p16(INK4a))in Cancer", EBioMedicine, 8, pp.30~39 (2016)
- Cicenas J, "CDK inhibitors and FDA: approved and orphan", Cancers (Basel), 16, pp.1555~ (2024)
- Sager RA, "Therapeutic potential of CDK4", 6inhibitors in renal cell carcinoma, 2022, pp.19, 305~320
- Dang CV, "MYC on the path to cancer", Cell, 149, pp.22~35 (2012)
- Chen H, "Targeting oncogenic Myc as a strategy for cancer treatment", Signal Transduct Target Ther, 3, pp.5~ (2018)
- Garralda E, "MYC targeting by OMO-103 in solid tumors : a phase 1 trial", Nat Med, 30, pp.762~771 (2024)
- Llombart V, "Therapeutic targeting of"undruggable"MYC", EBioMedicine, 75, pp.103756~ (2022)
- Wohlrab C, "The association between ascorbate and the hypoxia-inducible factors in human renal cell carcinoma requires a functional von Hippel-Lindau protein", Front Oncol, 8, pp.574~ (2018)
- Zhu Y, "STING : a master regulator in the cancer-immunity cycle", Mol Cancer, 18, pp.152~ (2019)
- Lin Z, "Clinical significance of STING expression and methylation in lung adenocarcinoma based on bioinformatics analysis", Sci Rep, 12, pp.13951~ (2022)
- Xia T, "Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis", Cell Rep, 14, pp.282~297 (2016)
- Parkes EE, "The clinical and molecular significance associated with STING signaling in breast cancer", NPJ Breast Cancer, 7, pp.81~ (2021)
- Gan Y, "The cGAS", STING pathway : a novel target for cancer therapy, 2021, pp.12, 795401~
- Kim Y, "Prognostic significance of STING expression in solid tumor : a systematic review and metaanalysis", Front Oncol, 13, pp.1244962~ (2023)
- Marletta S, "STING is a prognostic factor related to tumor necrosis, sarcomatoid dedifferentiation, and distant metastasis in clear cell renal cell carcinoma", Virchows Arch, 483, pp.87~96 (2023)
- Yan H, "The cGAS-STING pathway : a therapeutic target in chromosomally unstable cancers", Signal Transduct Target Ther, 8, pp.45~ (2023)
- Yao H, "STING promotes proliferation and induces drug resistance in colorectal cancer by regulating the AMPK-mTOR pathway", J Gastrointest Oncol, 13, pp.2458~2471 (2022)
