Loss of MSH2 protein expression is a risk factor in early stage cervical cancer

Nijhuis, Esther R.; Nijman, Hans W.; Oien, Karin A.; Bell, Alison M.; Hoor, Klaske A. ten; Reesink-Peters, Nathalie; Boezen, H. Marike; Hollema, Harry; Zee, Ate G.J. van der

doi:10.1136/jcp.2005.036038

Cited by 19 publications

(14 citation statements)

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“… 10 – 12 According to prior studies, lack of MSH2 or/and MLH1 is a common phenomenon in cervical intraepithelial neoplasia and cervical cancer. 13 , 14 The MSI of cervical cancer was 6.1% in this study, which was consistent with the report by Ercoli et al, 15 but was less than the 12.6% reported by Baay et al 16 We reason that the source of cases and single-nucleotide-repeat markers may lead to these variations. In the study, the ratio of dMMR was 25.8% and the rates of dMMR varied greatly when analyzed in subtypes with different childbearing history, abortion history, and tumor differentiation.…”

Section: Discussionsupporting

confidence: 91%

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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Section: Discussionsupporting

confidence: 91%

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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“…DNA mismatch repair proteins were found as important GOBP. Among these proteins, we found MSH2 which is among the routine IHC markers to identify microsatellite instability . Interestingly, its loss of expression is usually a risk factor in early stage cervical cancer .…”

Section: Resultsmentioning

confidence: 90%

Microproteomic Profiling of High‐Grade Squamous Intraepithelial Lesion of the Cervix: Insight into Biological Mechanisms of Dysplasia and New Potential Diagnostic Markers

Pottier

Kriegsmann

Alberts

et al. 2018

Proteomics Clinical Apps

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“…We concluded that TMA samples are a good representation of the full sections and therefore useful as a research tool in the screening of markers for their predictive and prognostic potential. 22 Immunostaining was semiquantitatively scored based on the intensity of nuclear or cytoplasmic staining. Intensity of immunostaining for receptor expression was scored as negative (0), weak (1+), positive (2+), or strongly positive (3+) staining.…”

Section: Analysis Of Immunostaining On Tmamentioning

confidence: 99%

Aromatase, Cyclooxygenase 2, HER-2/neu, and P53 as Prognostic Factors in Endometrioid Endometrial Cancer

Jongen¹,

Briët²,

Jong³

et al. 2009

International Journal of Gynecological Cancer

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The prognostic value of aromatase, cyclooxygenase 2 (COX-2), HER-2/neu, and p53 expression was determined in endometrioid endometrial cancer. Tissue microarrays were constructed comprising samples from 315 endometrioid endometrial cancer patients. Expression of aromatase, COX-2, HER-2/neu, and p53 was determined by immunostaining and related to classical clinicohistopathologic parameters, in addition to recurrence of disease and survival. Median follow-up time for all patients was 5.0 years. Patients were classified as Fédération Internationale de Gynécologie Obstétrique stage I (59.0%), stage II (17.1%), stage III (19.4%), and stage IV (4.1%). Sixty-five patients (20.6%) developed recurrent disease, and 38 (12.1%) died because of endometrial cancer. Aromatase, COX-2, HER-2/neu, and p53 expression was observed in 133 (42.2%), 107 (34.0%), 17 (5.4%), and 21 (6.7%) tumor cases, respectively. Aromatase expression in tumor cells was related to aromatase expression in stromal cells (P < 0.0001) and to HER-2/neu expression in tumor cells (P = 0.019). Aromatase expression in tumor as well as stromal cells was related to a low stage of disease (P = 0.02 and P = 0.001, respectively), whereas aromatase expression in stromal cells was also related to a low tumor grade (P = 0.021). P53 expression was related to a high stage and a high grade (P = 0.006 and P < 0.0001, respectively). In multivariate analysis, p53 overexpression was independently related to death because of the disease (P = 0.043; odds ratio 3.0; 95% confidence interval, 1.0-8.7). For COX-2, HER-2/neu, and aromatase, no relation with any other histopathologic parameter or survival was found. In conclusion, aromatase and p53 expression are related to tumor grade and stage of disease, whereas p53 is an independent prognostic factor in endometrioid endometrial cancer.

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Loss of MSH2 protein expression is a risk factor in early stage cervical cancer

Cited by 19 publications

References 38 publications

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

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

Microproteomic Profiling of High‐Grade Squamous Intraepithelial Lesion of the Cervix: Insight into Biological Mechanisms of Dysplasia and New Potential Diagnostic Markers

Aromatase, Cyclooxygenase 2, HER-2/neu, and P53 as Prognostic Factors in Endometrioid Endometrial Cancer

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