Immunohistochemical detection of hMLH1 and hMSH2 proteins in vulvar carcinoma

Kwaśniewska, Anna; Postawski, Krzysztof; Goździcka-Józefiak, Anna; Zdunek, Małgorzata; Korobowicz, Elzbieta; Miturski, R

doi:10.3892/ijmm.15.6.955

Cited by 3 publications

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“…Generally, MSI is associated with downregulation of MLH1, MSH2 and MSH6 expression. Although we did not determine the expression of the protein products of MMR genes immunohistochemically, our observations are in line with the previous findings of Kwasniewska et al (5). These authors did not observe a decrease in hMSH2 and hMLH1 protein expression, i.e.…”

Section: Discussionmentioning

confidence: 99%

Lack of microsatellite instability in squamous cell vulvar carcinoma

Bujko¹,

Kowalewska²,

Zub³

et al. 2012

Acta Obstet Gynecol Scand

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Mutator phenotypes with microsatellite instability (MSI) are observed in a subset of solid tumors. The objective of our study was to investigate the occurrence of MSI in vulvar squamous cell carcinoma (VSCC) and a possible relation between MSI and the presence of human papilloma virus (HPV). DNA samples from 44 tissue specimens of the primary VSCC as well as from six metastatic lymph node samples were analysed and compared with matched reference DNA from blood samples. The MSI status was examined by polymerase chain reaction (PCR) using the Bethesda panel of five microsatellite markers. PCR products were analysed by fluorescent capillary electrophoresis. No microsatellite instability was detected in tumor samples or in metastatic lymph nodes from any of the VSCC patients examined. Microsatellite instability seems not to play a major role in the carcinogenesis of VSCC and is probably not associated with the HPV-related genetic background of this neoplasm.

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Section: Discussionmentioning

confidence: 99%

Lack of microsatellite instability in squamous cell vulvar carcinoma

Bujko¹,

Kowalewska²,

Zub³

et al. 2012

Acta Obstet Gynecol Scand

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Enhanced Detection of Microsatellite Instability and Mismatch Repair Gene Expression in Cutaneous Squamous Cell Carcinomas

et al. 2006

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The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance

Feng¹,

Ji²,

Yue³

et al. 2018

CMAR

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BackgroundAccording to recent clinical observations, deficient DNA mismatch repair (dMMR) is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable.MethodsSixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs) was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI), including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR) groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups.ResultsOf the patient samples, 25.8% were associated with dMMR. PD-L1 in cancer cells, PD-L1 in TILs, and PD-1 in TILs took up 59.1%, 47.0%, and 60.6%, respectively. The data indicated that both dMMR and PD-L1 overexpression resulted from lower cancer differentiation, more incidences of childbearing, and a history of abortion. Abortion could significantly increase PD-1 expression levels in TILs. Additionally, more incidence of childbearing or older age (35–55 years) was able to upregulate PD-L1 expression in TILs. Statistical difference of PD-L1 in cancer cells could be observed between dMMR and pMMR subgroups. In the dMMR group, PD-L1 in cancer cells and PD-1 in TILs had no correlation (rs=0.161, p=0.537), but in the pMMR group, they had good correlation (rs=0.645, p<0.001).ConclusionAccording to prior studies and our own experiments, PD-L1 in both cancer cells and TILs and PD-1 in TILs are widely observed in cervical cancer patients, indicating that there may be potential to apply PD-1/PD-L1 antibody drugs in cervical cancer. dMMR patients are associated with higher PD-L1 expression compared with pMMR ones, which suggested that PD-1/PD-L1 antibody drugs may work well in dMMR cervical cancer patients. Moreover, in patients with more incidences of childbearing or abortion, dMMR may be a molecular detection target for clinical application of PD-1/PD-L1 antibody drugs.

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Immunohistochemical detection of hMLH1 and hMSH2 proteins in vulvar carcinoma

Cited by 3 publications

References 0 publications

Lack of microsatellite instability in squamous cell vulvar carcinoma

Lack of microsatellite instability in squamous cell vulvar carcinoma

Enhanced Detection of Microsatellite Instability and Mismatch Repair Gene Expression in Cutaneous Squamous Cell Carcinomas

The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance

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