chondroitin-sulfates and Carcinoma-in-Situ

The identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of the main principles in cancer development and growth, but has been largely neglected in preinvasive lesions. This is the first study addressing the involvement of the ECM in the "step-by-step" transition of normal fallopian tube epithelium into preinvasive lesions, and eventually the progression of preinvasive lesions into invasive HGSC.. The expression of highly sulfated chondroitin sulfate (CS-E), a characteristic glycosaminoglycan of the cancer-associated ECM, was assessed by immunohistochemistry in a large cohort of precursor lesions of the full spectrum of HGSC development, including 97 serous tubal intraepithelial carcinomas (STICs), 27 serous tubal intraepithelial lesions, and 24 p53 signatures. In addition, the immunological reactivity in the microenvironment was evaluated.. Increased stromal expression of highly sulfated CS-E was observed in 3.7%, 57.7%, and 90.6% of serous tubal intraepithelial lesions, STICs, and invasive HGSCs, respectively (P < 0.001). No or limited expression was found in p53 signatures and normal tubal epithelium (compared with STIC, P < 0.001). A gradual increase in the amount of CS-E expression between STIC and paired HGSC was demonstrated. Intense stromal CS-E expression in STIC was significantly associated with an immune infiltrate (P < 0.001).. Our study showed that increased stromal CS-E expression is related to the degree of the tubal epithelium abnormality. Specific alterations in the ECM (ie, CS-E expression) occur early in pelvic HGSC development and may represent a novel biomarker of early cancer progression, useful for the identification of novel clinical strategies.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Chondroitin Sulfates; Cohort Studies; Cystadenocarcinoma, Serous; Extracellular Matrix; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; Middle Aged; Neoplasm Grading; Precancerous Conditions

Chondroitin 6-sulphate is a glycosaminoglycan component of both cell membrane and basement membrane proteoglycans. In vitro it can inhibit tenascin, a molecule critical for epithelial cell migration during development and in wound healing. The immunohistochemical expression of chondroitin-6-sulphate and tenascin has been examined in 143 laryngeal biopsies from 38 patients, with particular attention to changes occurring with squamous cell carcinoma invasion. All tissues were formalin-fixed and paraffin-embedded. An avidin-biotin complex immunoperoxidase technique was used. Immunostaining for chondroitin-6-sulphate was seen in the basement membrane and/or cell membranes of basal and suprabasal cells of the laryngeal epithelium. Immunostaining of cell or basement membrane was seen at least focally in 67 of 71 (94 per cent) biopsies with no atypia, in 39 of 45 (87 per cent) biopsies with mild/moderate atypia, and in 16 of 16 (100 per cent) biopsies with severe dysplasia or carcinoma in situ (CIS); but in only 2 of 18 biopsies with invasion, although in neither of these was chondroitin-6-sulphate immunostaining seen at the actual site of invasion. Tenascin immunostaining was seen along the basement membrane in all biopsies. Those with CIS or invasion showed, in addition, strong tenascin staining of the adjacent stroma. The loss of chondroitin-6-sulphate immunostaining concurrent with squamous cell carcinoma invasion in the larynx suggests that loss of a chondroitin-6-sulphate-containing proteoglycan, or a change in proteoglycan side-chain composition, is a critical step in laryngeal epithelial tumour invasion.

Topics: Biomarkers; Carcinoma in Situ; Carcinoma, Squamous Cell; Chondroitin Sulfates; Humans; Immunohistochemistry; Laryngeal Neoplasms; Male; Neoplasm Invasiveness; Tenascin