Tumour mismatch repair protein loss is associated with advanced stage in oral cavity squamous cell carcinoma

Vasan, Kartik; Satgunaseelan, Laveniya; Anand, Sunaina; Asher, Rebecca; Selinger, Christina; Low, Tsu-Hui Hubert; Clark, Jonathan; Gupta, Ruta

doi:10.1016/j.pathol.2019.08.005

Cited by 14 publications

(13 citation statements)

References 53 publications

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“…However, they did not find any genomic difference between younger patients and older patients (Pickering et al, 2014). Instability in the mismatch repair gene also showed no association with younger age in the context of smoking or alcohol exposure (Vasan et al, 2019). However, the development of OSCC in patients without smoking/alcohol exposure, and in those who are younger in age, has been less studied.…”

Section: Discussionmentioning

confidence: 94%

Prognostic significance of smoking and alcohol history in young age oral cavity cancer

et al. 2020

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Objective To assess prognostic factors of patients with operable oral cavity squamous cell carcinoma (OSCC), focusing on the associations with smoking/alcohol exposure and age. Materials and Methods A total of 247 patients with OSCC who received curative surgery ± adjuvant radiotherapy were analyzed. The patient subgroups were divided according to pretreatment smoking/alcohol exposure. Individuals aged 45 years or less were classified as younger patients. Results The median follow‐up was 52.2 months. The 5‐year locoregional progression‐free survival (LRFFS), distant metastasis‐free survival (DMFS), overall survival (OS), and cancer‐specific survival (CSS) rates were 85.2%, 88.3%, 78.1%, and 83.5%, respectively. An advanced stage, differentiation, and lympho‐vascular space invasion were significantly associated with lower OS and CSS. In a subgroup analysis of younger patients (n = 49), more smoking/alcohol exposure was significantly associated with better OS (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05–0.95, p = .043). With increasing age, the HR for smoking/alcohol exposure with respect to OS increased up to 11.59 (95% CI: 1.49–89.84, p = .019) in older patients. Conclusion Younger OSCC patients with non‐ or less smoking/alcohol exposure showed unfavorable outcomes. The prognostic significance of pretreatment smoking/alcohol exposure changed from favorable to detrimental with increasing age in operable OSCC.

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Section: Discussionmentioning

confidence: 94%

Prognostic significance of smoking and alcohol history in young age oral cavity cancer

et al. 2020

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“…The secondary aim of this study was to identify any association between MMR deficient tumors and metachronous tumors, with a view to gaining an insight into the presence of tumor predisposition phenotype. Interestingly, there was no association of MMR deficient HNcSCC with the development of multiple metachronous tumors unlike Muire–Torre syndrome or with oral cavity squamous cell carcinoma 10 …”

Section: Discussionmentioning

confidence: 96%

“…This includes malignancies associated with colorectal cancer, Muir-Torre syndrome, and oral cavity SCC. 9,10 The literature on the role of MMR in non-melanoma skin cancers is conflicting, with a wide array of methods utilized to test MMR systems across multiple cutaneous malignancies. [11][12][13] All of these studies including a small number of patients report exceedingly rare occurrences of MMR dysfunction in cutaneous SCC.…”

Section: Introductionmentioning

confidence: 99%

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Mismatch repair protein loss in cutaneous head and neck squamous cell carcinoma

Vasan

Anand

Satgunaseelan

et al. 2020

Journal of Surgical Oncology

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Background The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology‐agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors. Methods The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively. Results The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes. Conclusion A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC.

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“…The malfunction of MMR and the reduced expression of its proteins not only correlate with the progression from preneoplastic lesions to OSCC but also with the stage and the behavior of oral invasive malignancies. High hMSH2 ( Figure 3 (Ba)) and hMLH1 expression ( Figure 3 (Aa)) have been associated with a reduced depth of invasion, and the absence of perineural invasion [ 57 ], while MMR deficient tumors ( Figure 3 (Ab,Bb)) have shown higher rates of bone invasion and high pT stage, and the presence of metachronous neoplasms [ 67 ].…”

Section: Msi In Head and Neck Carcinogenesismentioning

confidence: 99%

The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review

Cilona

Locatello

Novelli

et al. 2020

Cancers

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The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.

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Tumour mismatch repair protein loss is associated with advanced stage in oral cavity squamous cell carcinoma

Cited by 14 publications

References 53 publications

Prognostic significance of smoking and alcohol history in young age oral cavity cancer

Prognostic significance of smoking and alcohol history in young age oral cavity cancer

Mismatch repair protein loss in cutaneous head and neck squamous cell carcinoma

The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review

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