PD-L1 expression, tumor-infiltrating lymphocytes, mismatch repair deficiency, EGFR alteration and HPV infection in sinonasal squamous cell carcinoma

Hongo, Takahiro; Yamamoto, Hidetaka; Jiromaru, Rina; Yasumatsu, Ryuji; Kuga, Ryosuke; Hashimoto, Kazuki; Matsuo, Masaki; Wakasaki, Takahiro; Tamae, Akihiro; Taguchi, Kenichi; Toh, Satoshi; Masuda, Munetaka; Nakagawa, Takashi

doi:10.1038/s41379-021-00868-w

Cited by 19 publications

(27 citation statements)

References 54 publications

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“…In gastric cancer, higher PD-L1 level (CPS≥1) had a significantly better PFS (progression free survival) and OS ( 35 ). In sinonasal squamous cell carcinoma, PD-L1 expression was significantly associated with worse OS ( 36 ). In our study, patients with PD-L1 expression had better DFS and OS than those without PD-L1 expression in stage I-II disease but not in stage III-IV disease, which was consistent with a previous study of ESCC ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma

et al. 2022

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BackgroundDNA mismatch repair (MMR) deficiency (dMMR) has been recognized as an important biomarker for immunotherapy in esophageal squamous cell carcinoma (ESCC), along with programmed death ligand 1 (PD-L1) expression and/or tumor-infiltrated lymphocytes (TILs). However, in ESCC, MMR protein assessment has not been well studied at present.MethodsA total of 484 ESCC tissues treated between 2007 and 2010, in our hospital, were enrolled. Immunohistochemical expression of MLH1, MSH2, MSH6, PMS2, and PD-L1 on tissue microarray specimens and clinicopathological features, including TILs, were analyzed retrospectively.ResultsOut of the 484 studied cases, loss of MLH1, MSH2, MSH6, and PMS2 expression were found in 6.8%, 2.1%, 8.7%, and 4.8% patients, respectively. dMMR was found in 65 patients, 37 cases involved in one MMR protein, 17 cases involved in two proteins, 7 cases involved in three proteins, and 4 cases involved in four proteins. There was no significant survival difference between pMMR (MMR-proficient) and dMMR patients (P>0.05). However, 224 patients with low PMS2 expression had better DFS and OS than 260 patients with high PMS2 expression (P=0.006 for DFS and 0.008 for OS), which was identified as an independent prognostic factor in multivariate analyses. Positive PD-L1 expression was detected in 341 (70.5%) samples. In stage I-II disease, patients with PD-L1 expression had better DFS and OS than those without PD-L1 expression(P<0.05), which was not found in stage III-IV disease. With the ITWG system, 40.1% of cases were classified as high TILs. Patients in the high-TILs group tended to have better DFS (P=0.055) and OS (P=0.070) than those in the low-TILs group and the differences were statistically significant in pMMR, high MSH6, or PMS2 expression cases (P<0.05). Also, high PMS2 expression patients with both PD-L1 expression and high TILs, had similar DFS and OS compared with low PMS2 expression patients (P>0.05), which were much better than other high PMS2 expression patients.ConclusionThe expression level of MMR proteins could also be used as a prognostic factor in ESCC and PMS2 expression outperformed other MMR proteins for predicting survival. The combination of PD-L1 expression and TILs may lead to more efficient risk stratification of ESCC.

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Section: Discussionmentioning

confidence: 99%

PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma

et al. 2022

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“…So far, only a few studies have addressed the MSI/MMR status in sinonasal carcinomas, with a resulting frequency of MSI for ITACs of 2% and between 2–21% in dMMR/MSI for SNSCCs [ 63 , 64 , 65 , 66 ]. Although dMMR/MSI-H SNSCCs are a small subgroup of SNSCC, they are clearly molecularly defined and they are most likely sensitive to ICIs.…”

Section: Discussionmentioning

confidence: 99%

Mismatch Repair Deficiency and Somatic Mutations in Human Sinonasal Tumors

Hieggelke

Heydt

Castiglione

et al. 2021

Cancers

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Due to limitations in local therapy approaches for sinonasal tumors, improvement in systemic therapies plays a pivotal role for prolongation of the patient’s survival. The aim of this study was to examine potential biomarkers, including deficiency in mismatch repair proteins (dMMR)/microsatellite instability (MSI-H) in sinonasal cancers and their precancerous lesions. A comprehensive analysis of 10 sinonasal cancer cell lines by whole exome sequencing, screening 174 sinonasal tumors by immunohistochemistry (IHC) for mismatch repair deficiency and next generation sequencing (NGS) of 136 tumor samples revealed a dMMR/MSI-H sinonasal squamous cell carcinoma (SNSCC) cell line based on a somatic missense mutation in MLH1 and an overall frequency of dMMR/MSI-H SNSCC of 3.2% (4/125). Targetable EGFR mutations were found in 89.3% (25/28) of inverted sinonasal papilloma (ISP) and in 60% (6/10) of ISP-associated carcinomas. While PIK3CA and EGFR mutations were not mutually exclusive, KRAS mutated tumors were an EGFR-wildtype. The effect of potential driver mutations in FGFR2, FGFR3, BRAF, HRAS, MAP2K1, PTEN, NOTCH1 and CARD11 need further investigation. Our results suggest that biomarker testing, including MMR-IHC and NGS panel analysis, should be integrated into the diagnostics of clinically aggressive ISPs and SNSCC to assess prognosis and facilitate therapeutic decisions.

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“…Data regarding the clinical importance of molecular characterization of SNSCC are beginning to emerge. Although the clinical evaluation of the efficacy of immune checkpoint inhibitors in sinonasal cancer is still in its early phases, preliminary data indicate that response to treatment may be associated not only to immune marker status (i.e., PDL1 expression, tumor infiltrating lymphocytes and tumor microenvironment subtype) but also to tumor genotypes [58]. Specifically, SNSCCs with EGFR mutation showed an unfavorable response to treatment with immune checkpoint inhibitors, whereas in patients with EGFR wild type SNSCC this treatment significantly improved the overall survival [58].…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

“…Although the clinical evaluation of the efficacy of immune checkpoint inhibitors in sinonasal cancer is still in its early phases, preliminary data indicate that response to treatment may be associated not only to immune marker status (i.e., PDL1 expression, tumor infiltrating lymphocytes and tumor microenvironment subtype) but also to tumor genotypes [58]. Specifically, SNSCCs with EGFR mutation showed an unfavorable response to treatment with immune checkpoint inhibitors, whereas in patients with EGFR wild type SNSCC this treatment significantly improved the overall survival [58]. Thus, it is likely that in the near future molecular characterization of SNSCC, will become part of the routine assessment of these tumors, in order to support the choice of the best treatment option.…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

Taverna

Agaimy

Franchi

2022

Cancers

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Sinonasal carcinomas are a heterogeneous group of rare tumors, often with high-grade and/or undifferentiated morphology and aggressive clinical course. In recent years, with increasing molecular testing, unique sinonasal tumor subsets have been identified based on specific genetic alterations, including protein expression, chromosomal translocations, specific gene mutations, or infection by oncogenic viruses. These include, among others, the identification of a subset of sinonasal carcinomas associated with HPV infection, the identification of a subset of squamous cell carcinomas with EGFR alterations, and of rare variants with chromosomal translocations (DEK::AFF2, ETV6::NTRK and others). The group of sinonasal adenocarcinomas remains very heterogeneous at the molecular level, but some recurrent and potentially targetable genetic alterations have been identified. Finally, poorly differentiated and undifferentiated sinonasal carcinomas have undergone a significant refinement of their subtyping, with the identification of several new novel molecular subgroups, such as NUT carcinoma, IDH mutated sinonasal undifferentiated carcinoma and SWI/SNF deficient sinonasal malignancies. Thus, molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this review, we summarize the recent developments in the molecular characterization of sinonasal carcinomas and we discuss how these findings are likely to contribute to the classification of this group of rare tumors, with a focus on the potential new opportunities for treatment.

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PD-L1 expression, tumor-infiltrating lymphocytes, mismatch repair deficiency, EGFR alteration and HPV infection in sinonasal squamous cell carcinoma

Cited by 19 publications

References 54 publications

PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma

PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma

Mismatch Repair Deficiency and Somatic Mutations in Human Sinonasal Tumors

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

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