Value of Tenascin‐C content and association with clinicopathological parameters in uterine cervical lesions

Abstract

To determine whether the content of the matrix protein tenascin-C (Tn-C) is of diagnostic or prognostic value in cervical lesions, we evaluated increases in Tn-C immunoreactivity in 80 formalin-fixed, paraffin-embedded biopsies and surgical specimens of the uterine cervix. Tn-C content in the basement membrane zone and in the stroma was graded and compared to some prognostic parameters. In the normal cervix, Tn-C formed a thin continuous band. In cervicitis, Tn-C bands thickened in the basement membrane zone and the adjacent stroma in the form of thin filaments. In 30 squamous intraepithelial lesions (SILs) of various grades, Tn-C bands were either slightly (1؉) or moderately (2؉) thickened in the basement membrane zone, while slight stromal Tn-C immunoreactivity in the form of thin bands was observed in 12 cases, regardless of grade and inflammatory stromal reaction. In invasive carcinoma, Tn-C content was markedly increased in the stroma and around the invasive nests of tumors. The intensity of Tn-C immunoreactivity was significantly higher in grade I tumors than in others (p < 0.04). The intensity of increase in Tn-C immunoreactivity was 10.5-fold (95% CI 3.39 -32. Key words: tenascin-C; uterine cervix; clinicopathologic parameters; grade; prognosisThe invasion and metastatic progression of cervical cancer is greatly dependent on local interactions with adjacent cells and tissue. 1 The process involves complex changes in normal epithelial cell-cell and epithelial cell-mesenchymal stromal interactions. 2 In addition to integrins and cellular adhesion molecules, extracellular glycoproteins, such as fibronectins, laminins and tenascins, may be involved in the complex biologic cascade of cancer invasion and metastasis. In the etiology, progression and metastasis of cancer, the microenvironment of the local host tissue can be an active participant. 1,3,4 Specialized cells of developing multicellular organisms are surrounded by a complex extracellular matrix (ECM), comprised largely of different collagens, proteoglycans and glycoproteins. This ECM is a substrate for tissue morphogenesis, lending support and flexibility to mature tissues. Tenascin-cytotactin (Tn-C), a large glycoprotein of the ECM, displays highly restricted and dynamic patterns of expression in the embryo, particularly during neural development, skeletogenesis and vasculogenesis. This molecule is reincreased in the adult during normal processes such as wound healing, nerve regeneration and tissue involution and in pathologic states including vascular disease, tumorigenesis and metastasis. 5 The stroma and its ECM located in and around invasive tumors may show a desmoplastic reaction that differs morphologically from that of the normal stroma of the same organ. There is evidence that this desmoplastic reaction is related to tumor invasion and is the result of a derangement of cell-cell adhesion. As Tn-C is an important component of the desmoplastic reaction, its content may be an index of the invasive potential of a malignant tumor. 3 In invasive b...

Tenascins: regulation and putative functions during pathological stress

“…This was particularly recognized in the cases of prominent tenascin-C staining at the invasion borders [130][131][132]. Similar findings were made for uterine and ovarian cancers where intense stromal tenascin-C staining was found in malignant tumours [133,134]. However, in one report it was noted that despite a high percentage of strong tenascin-C staining in invasive cancers, the few tenascin-C-negative invasive cases appeared to have an even worse prognosis [135].…”

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

“…45 Tenascin-C expression is markedly increased in invasive cervical carcinoma and oral SCC, but the role of TENX in tumorigenesis is largely unknown. 46,47 Collagens are triple-helix proteins formed by the association of three polypeptide chains that are coded by different genes of the same collagen type. 48 Vertebrates have 28 different types of collagens that provide tissue-specific structure and function by assembling into a variety of supramolecular structures of the extracellular matrix.…”

Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder

“…Tumour associated changes in Tn-C expression at all could be proved as prognostic relevant for several tumour entities (Emoto et al 2001;Wiksten et al 2003;Tanaka et al 2000;Buyukbayram and Arslan 2002).…”