Mutations of microsatellite instability target genes in sporadic basal cell carcinomas

Saetta, Angelica A.; Stamatelli, Angeliki; Κάρλου, Μαρία; Michalopoulos, Nikolaos V.; Patsouris, Efstratios; Aroni, Kyriaki

doi:10.1016/j.prp.2007.08.009

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…These results contrasted to those found in immunocompetent patients where AMLs and (non-Muir-Torre related) SGCs are microsatellite stable (Rimsza et al, 2000;Harwood et al, 2001). As less than 5% of the cutaneous SCCs and BCCs in immunocompetent patients display MSI (Quinn et al, 1995;Gray et al, 2006;Saetta et al, 2007), we hypothesized that cutaneous skin carcinomas of this specific group of patients might display MSI as a result of the azathioprine treatment. This could also be a possible explanation for the higher incidence of SCCs observed in azathioprine-using OTRs compared to OTRs on other drugs (Ulrich and Stockfleth, 2007;Crespo-Leiro et al, 2008).…”

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confidence: 62%

Azathioprine-Induced Microsatellite Instability Is Not Observed in Skin Carcinomas of Organ Transplant Recipients

Wisgerhof

Hameetman

Tensen

et al. 2009

Journal of Investigative Dermatology

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subsequently underreported. We recommend to carefully examine the skin of patients, particular with red hair or a fair skin color, for the presence of nonpigmented, white to pale red macules with a silvery ''shining'' when observed with tangential light.Finally, although our single case does not allow definitive conclusions about the association of MC1R polymorphism with ''white'' nevi and ''red'' melanomas, it represents an interesting observation for future investigations.

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confidence: 62%

Azathioprine-Induced Microsatellite Instability Is Not Observed in Skin Carcinomas of Organ Transplant Recipients

Wisgerhof

Hameetman

Tensen

et al. 2009

Journal of Investigative Dermatology

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“…None of the 141 analyzed skin lesions displayed MSI at any of the assessed markers [ 20 ]. Based on their results and the data reported in previous studies, the authors concluded that MSI-H/dMMR is not a relevant tumorigenic mechanism in non-melanoma skin cancer [ 20 , 21 , 22 ]. By contrast, MSI-H/dMMR might be more relevant in cutaneous melanoma (CM) and its responsiveness to ICI.…”

Section: Discussionmentioning

confidence: 89%

Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma

Gambichler

Rached

Tannapfel

et al. 2021

Cancers

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We aimed to assess for the first time the mismatch repair (MMR) protein expression in Merkel cell carcinoma (MCC). Immunohistochemistry was performed for MLH1, MSH2, MSH6, and PMS2 on patients’ tumor tissue (n = 56), including neighbored healthy control tissue. In cases with low-level MMR expression (<10th percentile), we performed multiplex PCR in combination with high-resolution capillary electrophoresis in order to confirm microsatellite instability (MSI). Microscopic evaluation revealed a high median expression for all MMR proteins studied (91.6–96.3%). However, six patients (56/10.7%) had low-level MLH1 expression, six (55/10.9%) had low-level MSH2 expression, five (56/8.9%) had low-level MSH6 expression, and six (54/11.1%) had low-level PMS2 expression. Together, we observed nine (56/16.1%) patients who had low-level MMR expression of at least one protein. Of the patients with low-level MMR expression, MSI evaluation was possible in five cases, revealing one case with high-level MSI. In all MMR proteins assessed, low-level expression was significantly (p = 0.0004 to p < 0.0001) associated with a negative Merkel cell polyomavirus (MCPyV) status. However, the expression profiles of the MMR proteins did not correlate with clinical outcome measures such as disease relapse or death (p > 0.05). MCC appears to be a malignancy characterized by low-level MMR rather than completely deficient MMR in a subset of cases, predominantly affecting MCPyV-negative tumors. Future studies will establish whether this subset of MCC patients respond better to immune checkpoint inhibitor therapy.

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“…However, none of the skin lesions showed MSI-H at any of the assessed markers [ 11 ]. Based on their results and the data reported in the previous studies [ 5 , 6 , 7 , 8 , 9 ], the authors concluded that MSI-H/dMMR is not a relevant tumorigenic mechanism in NMSC [ 9 ]. Young et al [ 12 ] found overexpression of MMR proteins in cSCC when compared to normal epidermis.…”

Section: Discussionmentioning

confidence: 98%

“…However, there exist relatively sparse and conflicting data on MSI-H/dMMR in cutaneous malignancies. Several research groups previously investigated MSI-H in NMSC [ 5 , 6 , 7 , 8 , 9 ], also including 56 cSCC. Notably, 53 (56/94.6%) lesions originated from immunosuppressed patients.…”

Section: Introductionmentioning

confidence: 99%

Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma

et al. 2021

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There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen’s disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.

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Mutations of microsatellite instability target genes in sporadic basal cell carcinomas

Cited by 6 publications

References 24 publications

Azathioprine-Induced Microsatellite Instability Is Not Observed in Skin Carcinomas of Organ Transplant Recipients

Azathioprine-Induced Microsatellite Instability Is Not Observed in Skin Carcinomas of Organ Transplant Recipients

Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma

Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma

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