High levels of soluble <scp>MICA</scp> are significantly related to increased disease‐free and disease‐specific survival in patients with cervical adenocarcinoma

Samuels, Sanne; Ferns, Debbie M.; Meijer, Dennis; Straalen, Jan P. van; Buist, Marrije R.; Zijlmans, Henry; Kenter, Gemma G.; Jordanova, Ekaterina S.

doi:10.1111/tan.12562

Cited by 19 publications

(17 citation statements)

References 51 publications

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“…While it is well known that SCC and UCAC present different molecular profiles [32], as well as distinctive pathogenesis and clinical behavior, the current treatment regimens are still relatively the same for both histologically different cervical cancers; these conventionally involve surgery, radiotherapy, and chemotherapy. In line with the above, there is significant evidence that UCAC have a greater propensity to metastasis and have worse prognosis, than SCC [6,33]. Thus, it is feasible to (10x, 20x, 40x, and 63x) from a cervicitis sample.…”

Section: Discussionmentioning

confidence: 66%

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer

et al. 2020

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Background: B7-H6 has been revealed as an endogenous immunoligand expressed in a variety of tumors, but not expressed in healthy tissues. Heretofore, no studies have been reported describing B7-H6 in women with cervical cancer. To investigate this question, our present study was conducted. Results: This retrospective study comprised a total of 62 paraffinized cervical biopsies, which were distributed in five groups: low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), squamous cervical carcinoma (SCC), uterine cervical adenocarcinoma (UCAC), and a group of cervicitis (as a control for non-abnormal/non-transformed cells). Cervical sections were stained by immunohistochemistry to explore the expression of B7-H6, which was reported according to the immunoreactive score (IRS) system. We observed a complete lack of B7-H6 in LSIL abnormal epithelial cells. Interestingly, B7-H6 began to be seen in HSIL abnormal epithelial cells; more than half of this group had B7-H6 positive cells, with staining characterized by a cytoplasmic and membranous pattern. B7-H6 in the SCC group was also seen in the majority of the sections, showing the same cytoplasmic and membranous pattern. Strong evidence of B7-H6 was notably found in UCAC tumor columnar cells (in 100% of the specimens, also with cytoplasmic and membranous pattern). Moreover, consistent B7-H6 staining was observed in infiltrating plasma cells in all groups. Conclusions: B7-H6 IRS positively correlated with disease stage in the development of cervical cancer; additionally, B7-H6 scores were found to be even higher in the more aggressive uterine cervical adenocarcinoma, suggesting a possible future therapeutic target for this cancer type.

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Section: Discussionmentioning

confidence: 66%

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer

et al. 2020

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“…32 Indeed, previous studies showed that peripheral blood monocytes are the predominant cells secreting HLA-G5. 33 In this study, the relatively large number of CRC patients included in our evaluation (n 5 133) allowed for investigation of the prognostic value of plasma sHLA-G. Several clinical studies found no correlation between sHLA-G concentration in plasma/serum and clinical parameters including overall survival and disease free survival in cervical cancer, 34 esophageal squamous cell carcinoma 35 and melanoma patients. 33 On the other hand, in non-small-cell lung cancer patients with squamous cell carcinoma it was shown that high levels of sHLA-G is significantly associated with shorter overall survival.…”

Section: Discussionmentioning

confidence: 92%

Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages

et al. 2017

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The expression of HLA-G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA-G (sHLA-G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10 to 15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA-G levels in CRC patients, preoperative plasma sHLA-G levels were determined by ELISA in CRC patients (n = 133). In addition, the local expression of HLA-G in tumour biopsies was assessed using tissue microarray analysis (n = 255). Within the high 33rd percentile of sHLA-G levels (265-890 U/mL; n = 44) we observed higher frequency of MC patients (p = 0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (p = 0.035; two-tailed t-test). Moreover, MC patients had significantly higher sHLA-G levels compared to those with adenocarcinoma not otherwise specified (p = 0.036; two-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA-G levels and liver metastasis free survival (LMFS) (p = 0.041; R = -0.321), in stage III patients high sHLA-G levels were associated with significantly longer LMFS (p = 0.002), and sHLA-G levels displayed positive correlation with LMFS (p = 0.006; R = 0.409). High HLA-G expression in tumours was associated with poor cancer specific overall survival in stage II to III (p = 0.01), and with shorter LMFS in stage II patients (p = 0.004). Our findings reveal that sHLA-G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC.

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“… 1 , 2 Several types of cervical tumor histology can be distinguished, but the most commonly applied stratification is squamous cell carcinoma vs adenocarcinoma, both with different oncogenic mutations, 3 , 4 and different immunological tumor microenvironment. 5 , 6 , 7 Despite these substantial differences, current treatment modalities are the same for both squamous cell carcinomas and adenocarcinomas. 8 At present, patients with cervical cancer are treated with radical hysterectomy and pelvic lymphadenectomy or chemoradiation, depending on tumor stage and tumor size.…”

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confidence: 99%

Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix

et al. 2016

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Programmed death-ligand 1 (PD-L1) is expressed in various immune cells and tumor cells, and is able to bind to PD-1 on T lymphocytes, thereby inhibiting their function. At present, the PD-1/PD-L1 axis is a major immunotherapeutic target for checkpoint inhibition in various cancer types, but information on the clinical significance of PD-L1 expression in cervical cancer is largely lacking. Here, we studied PD-L1 expression in paraffin-embedded samples from two cohorts of patients with cervical cancer: primary tumor samples from cohort I (squamous cell carcinoma, n=156 and adenocarcinoma, n=49) and primary and paired metastatic tumor samples from cohort II (squamous cell carcinoma, n=96 and adenocarcinoma, n=31). Squamous cell carcinomas were more frequently positive for PD-L1 and also contained more PD-L1-positive tumor-associated macrophages as compared with adenocarcinomas (both P<0.001). PD-L1-positive tumor-associated macrophages were found to express CD163 and/or CD14 by triple fluorescent immunohistochemistry, demonstrating an M2-like phenotype. Interestingly, disease-free survival (P=0.022) and disease-specific survival (P=0.046) were significantly poorer in squamous cell carcinoma patients with diffuse PD-L1 expression as compared with patients with marginal PD-L1 expression (i.e., on the interface between tumor and stroma) in primary tumors. Disease-specific survival was significantly worse in adenocarcinoma patients with PD-L1-positive tumor-associated macrophages compared with adenocarcinoma patients without PD-L1-positive tumor-associated macrophages (P=0.014). No differences in PD-L1 expression between primary tumors and paired metastatic lymph nodes were detected. However, PD-L1-positive immune cells were found in greater abundance around the metastatic tumors as compared with the paired primary tumors (P=0.001 for squamous cell carcinoma and P=0.041 for adenocarcinoma). These findings point to a key role of PD-L1 in immune escape of cervical cancer, and provide a rationale for therapeutic targeting of the PD-1/PD-L1 pathway.

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High levels of soluble MICA are significantly related to increased disease‐free and disease‐specific survival in patients with cervical adenocarcinoma

Cited by 19 publications

References 51 publications

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer

Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages

Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix

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