Novel protein and immune response markers of human serous tubal intraepithelial carcinoma of the ovary

Article type: Research Article

Authors: Gutkin, Dmitriy W.^a | Shurin, Michael R.^{a; b} | El Azher, Mounia Alaoui^c | Shurin, Galina V.^b | Velikokhatnaya, Liudmila^c | Prosser, Denise^c | Shin, Namhee^d | Modugno, Francesmary^e | Stemmer, Paul^d | Elishaev, Esther^e | Lokshin, Anna^{a; c; e; *}

Affiliations: [a] Departments of Pathology, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA | [b] Departments of Immunology, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA | [c] Departments of Medicine, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA | [d] Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA | [e] Departments of Obstetrics and Gynecology, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

Correspondence: [*] Corresponding author: Anna Lokshin, Professor of Medicine, Pathology, Ob/Gyn %****␣cbm-26-cbm190528_temp.tex␣Line␣25␣**** University of Pittsburgh Cancer Institute, Hillman Cancer Center, UPCI Research Pavilion, Suite 1.19d, 5117 Centre Ave, Pittsburgh, PA 15213-1863, USA. Tel.: +1 412 403 5714; Fax: +1 412 623 1415; E-mail: [email protected].

Abstract: Ovarian cancer is the leading cause of death among gynecologic diseases in the USA and Europe. High-grade serous carcinoma (HGSC) of the ovary, the most aggressive type of ovarian cancer, is typically diagnosed at advanced stages when the 5-year survival is dismal. Since the cure rate for stage I HGSC is high, early detection of localized initial disease may improve patient outcomes. Serous tubal intraepithelial carcinoma (STIC) is considered to be a precursor lesion of HGSC. Discovery of biomarkers associated with STIC could aid in the development of an HGSC screening algorithm. Using immunohistochemical staining, we have demonstrated overexpression of UCHL1, ADAMTS13, and GAPDH in patients’ STIC lesions, but not in cancer-free fallopian tubes. We additionally demonstrated a marked increase of T cells in perineoplastic stroma surrounding STIC lesions (largely CD4 + cells), but not in normal fallopian tubes and HGSC. FOXP3 + T regulatory cells are absent in STIC lesions but are present in HGSC. These observations indicate the microenvironment surrounding a STIC lesion may be immune promoting in contrast to the immune suppressive microenvironment of invasive carcinoma. In summary, we have identified UCHL1, ADAMTS13, and GAPDH as novel potentially useful markers associated with early stages of HGSC tumorigenesis and possibly contribute to STIC immunogenicity. The lack of immune suppression in the STIC microenvironment indicates that the immune system can still recognize and keep STIC controlled at this stage of the tumor development.

Keywords: Ovarian cancer, high-grade serous carcinoma (HGSC), serous tubal intraepithelial carcinoma (STIC), biomarkers, immune response

DOI: 10.3233/CBM-190528

Journal: Cancer Biomarkers, vol. 26, no. 4, pp. 471-479, 2019