Loss of basement membrane components laminin and type IV collagen parallels the progression of oral epithelial neoplasia K I Tosios, N Kapranos* & S I Papanicolaou Division of Oral Pathology, Faculty of Dentistry, University of Athens, and *Pathology Laboratory, Diagnostic and Therapeutic Center ‘HYGEIA’, Athens, Greece Date of submission 13 February 1997 Accepted for publication 23 January 1998 Tosios K I, Kapranos N & Papanicolaou S I (1998) Histopathology 33, 261–268 Loss of basement membrane components laminin and type IV collagen parallels the progression of oral epithelial neoplasia Aims: To determine the immunohistochemical localiza- tion of basement membrane components laminin and type IV collagen in premalignant and malignant lesions of the oral epithelium. Methods and results: Formalin-fixed tissue sections of 12 epithelial hyperplasias with no dysplasia and 30 dysplasias, clinically diagnosed as leukoplakia and/or erythroplakia, as well as 50 invasive squamous cell carcinomas, were stained with mouse monoclonal antibodies to human laminin and type IV collagen. Statistical analysis showed that there was a linear trend for discontinuous distribution of laminin from epithelial hyperplasia to epithelial dysplasia and invasive squamous cell carcinoma (P < 0.001). Laminin staining showed a linear trend for discontinuity with increasing grade of dysplasia (P < 0.05) and was more frequently discontinuous in areas of deep tumour invasion than in central or superficial areas (P < 0.05). Brush-shaped thickening and reduplication of the basement mem- brane were also identified. Conclusions: Alterations in the distribution of laminin and type IV collagen in oral premalignant and malignant lesions indicate that the loss of continuity of the subepithelial basement membrane parallels the progression of the neoplastic transformation process in oral epithelium. Keywords: basement membrane, carcinoma, immunohistochemistry, laminin, leukoplakia, oral, squamous cell, type IV collagen Introduction Basement membranes are complex extracellular matrices of specialized structure and function, present in all vertebrate and most invertebrate animals. 1 They separate epithelial, endothelial and mesothelial cells from the underlying connective tissue, or surround vascular pericytes and muscle, adipose and Schwann cells. Unique components of basement membranes include type IV collagen, laminin, perlecan, nidogen/ entactin, type VII collagen and some minor or site- specific molecules. 2 Basement membranes participate in tissue development, growth, maintenance, repair and regeneration. 1 They provide structural support, form selective barriers and are involved in critical cellular functions such as movement, attachment, proliferation and differentiation. Neoplastic invasion and metastasis are characterized by the ability of tumour cells to cross tissue compart- ment boundaries. 3 The subepithelial basement mem- brane plays an important role in the complex interactions of this process, as it is the first obstacle to be traversed by the neoplastic cells. 3–6 In general, the subepithelial basement membrane is lost in most invasive carcinomas, whereas in benign lesions and in situ carcinomas its continuity is retained. The ability of malignant neoplasms to destroy the basement mem- brane has been related to their invasive potential, and utilized as an aid in the early diagnosis and prediction of the biological behaviour of various tumors. 5,7 Oral squamous cell carcinomas account for 5% of all cancers occurring in the human body and comprise Histopathology 1998, 33, 261–268  1998 Blackwell Science Limited. Address for correspondence: Dr K Tosios, Division of Oral Pathology, Faculty of Dentistry, 2, Thivon Street, 115 27 Athens, Greece.