Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

Corvigno, Sara; Wisman, G. Bea A.; Mezheyeuski, Artur; Zee, Ate G.J. van der; Nijman, Hans W.; Åvall‐Lundqvist, Elisabeth; Östman, Arne; Dahlstrand, Hanna

doi:10.18632/oncotarget.7613

Cited by 42 publications

(54 citation statements)

References 52 publications

(47 reference statements)

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“…The ovarian cancer cohort, including cases receiving or not receiving chemotherapy, is described in detail elsewhere (Corvigno et al , 2016). …”

Section: Methodsmentioning

confidence: 99%

“…Details concerning digital image analyses have been previously reported (Corvigno et al , 2016; Mezheyeuski et al , 2016). In short, the double-stained slides were scanned by a VSlide slide scanning microscope (Metasystems, Alltlussheim, Germany) using × 10 objective and RGB LED illumination for colour deconvolution.…”

Section: Methodsmentioning

confidence: 99%

“…A recent study found that high expression of PDGFR- β in perivascular cells in serous ovarian carcinoma was significantly correlated to worse outcome (Corvigno et al , 2016). In contrast, increased perivascular PDGFR- β in primary colorectal cancer was associated with shorter survival in subsequent metastatic disease (Mezheyeuski et al , 2016).…”

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confidence: 99%

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Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma

et al. 2016

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Background:Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-angiogenic treatment with multi-tyrosine-kinase-inhibitor, is used for first-line treatment of metastatic disease. Variations in vascular characteristics are likely to contribute to variations in intrinsic aggressiveness of the disease. Emerging studies are identifying perivascular status, including perivascular PDGFR-β, as a determinant of prognosis in other tumour types.Methods:This work explored the impact on prognosis of vascular characteristics in RCC through analyses of a population-based collection of tumours from surgery-alone-treated patients. The quantitative data from a panel of vascular metrics were obtained through computerised image analysis of sections double-stained for expression of the endothelial cell marker CD34 together with perivascular markers α-SMA or PDGFR-β.Results:Perivascular expression of PDGFR-β and α-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-β and α-SMA as well as low vessel density was significantly associated with short survival in uni- and multivariate analyses. Subgroup analyses demonstrated that the prognostic impact of the perivascular markers was particularly prominent in the T4-subgroup. A novel metric, related to PDGFR-β perivascular heterogeneity, was also associated with prognosis in uni-and multi-variate analyses. This novel metric also acted as a prognosis marker in ovarian cancer.Conclusions:The study demonstrates previously unrecognised associations between RCC survival and the absolute levels, and variability, of perivascular PDGFR-β. This marker should be further explored in other RCC cohorts. Findings also suggest mechanistic analyses and studies on the relationship between perivascular status and efficacy of multi-tyrosine-kinase-inhibitors.

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“…The ovarian cancer cohort, including cases receiving or not receiving chemotherapy, is described in detail elsewhere (Corvigno et al , 2016). …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma

et al. 2016

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“…Analyses of patients with primary breast cancer noted, as in this study, an association between low pericyte coverage, determined by NG2 IHC, and poor prognosis [10]. In contrast, the analyses of serous ovarian cancer and renal cell cancer patients identified a statistically significant relationship between high pericyte coverage (determined by PDGFR-β and α-SMA respectively) and poor prognosis [17, 26]. …”

Section: Discussionmentioning

confidence: 64%

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

et al. 2016

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Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-β or α-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-α and -β and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-α and -β remained independent factors for survival in multivariate analyses.Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-α and -β were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections.

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“…Ovarian cancer is one of the types of gynecological tumors that cause more deaths worldwide, presenting a low overall survival rate [1]. It is an insidious disease diagnosed in advanced stages.…”

Section: Introductionmentioning

confidence: 99%

Role of Alpha-Smooth Muscle Actin and Fibroblast Activation Protein Alpha in Ovarian Neoplasms

Silva¹,

Jammal²,

Etchebehere

et al. 2018

Gynecol Obstet Invest

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Background/Aims: Studies show that tumor growth is not just determined by the presence of malignant cells, since interactions between cancer cells and stromal microenvironment have important impacts on the cancer growth and progression. Cancer-associated fibroblasts play a prominent role in this process. The aims of the study were to investigate 2 cancer-associated fibroblasts markers, alpha-smooth muscle actin (α-SMA), and fibroblast activation protein alpha (FAP) in the stromal microenvironment of benign and malignant ovarian epithelial neoplasms, and to relate their tissue expression with prognostic factors in ovarian cancer. Methods: α-SMA and FAP were evaluated by immunohistochemistry in malignant (n = 28) and benign (n = 28) ovarian neoplasms. Fisher’s exact test was used with a significance level lower than 0.05. Results: FAP immunostaining was stronger in ovarian cancer when compared to benign neoplasms (p = 0.0366). There was no significant difference in relation to α-SMA expression between malignant and benign ovarian neoplasms as well as prognostic factors. In ovarian cancer, FAP stainings 2/3 was significantly related to histological grades 2 and 3 (p = 0.0183). Conclusion: FAP immunostaining is more intense in malignant neoplasms than in benign ovarian neoplasms, as well as in moderately differentiated and undifferentiated ovarian carcinomas compared to well-differentiated neoplasms, thus indicating that it can be used as a marker of worse prognosis.

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Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

Cited by 42 publications

References 52 publications

Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma

Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

Role of Alpha-Smooth Muscle Actin and Fibroblast Activation Protein Alpha in Ovarian Neoplasms

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