Expression of the 67 kD laminin receptor in human cervical preneoplastic and neoplastic squamous epithelial lesions: an immunohistochemical study

Interactions of cancer cells with laminin play a critical role during the progression of solid malignant tumours. Increased expression of the 67 kD laminin receptor (67LR), one of the several laminin binding proteins, is associated with the invasive and metastatic capacity of various types of cancer, including breast, colon, ovary, lung, and endometrial carcinoma. In this study, 67LR expression was analysed in a series of cervical biopsy specimens including 16 normal cervical tissues, 36 low‐grade squamous intraepithelial lesions (SILs), 24 high‐grade SILs, and 11 invasive carcinomas. Detection of the 67LR was performed using immunoperoxidase staining and the monoclonal antibody MLuC5 which specifically recognizes the 67LR. Immunostaining of the 67LR was correlated with human papillomavirus (HPV) type detected by in situ hybridization and with proliferative activity of the lesion determined by immunohistochemistry with the MIB‐1 monoclonal antibody, specific for the Ki67 antigen. Increased expression of the 67LR was correlated with the histological severity of the lesions, with the strongest immunoreactivity being found in invasive carcinomas. Significant differences in 67LR expression were found between normal cervical epithelium and high‐grade SILs (P<0·05, non‐parametric Mann‐Whitney test) or invasive carcinomas (P<0·001), as well as between low‐ or high‐grade SILs and invasive carcinoma (P<0·01 and P<0·05, respectively). Ki67 antigen expression also increased with the severity of the lesions. There was a positive correlation for each type of lesion between expression of the 67LR and of the Ki67 antigen. No specific relationship was found between 67LR or Ki67 antigen immunostaining and HPV type detected in SILs, segregated into low‐grade and high‐grade lesions. These data add weight to the evidence that increased expression of the 67LR is a consistent, but not sufficient feature of the invasive and metastatic phenotype and suggest that high expression of the 67LR might be associated with both more proliferative and more aggressive cervical (pre)neoplastic lesions. © 1997 John Wiley & Sons, Ltd.

[1]  R. Burk,et al.  Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. , 1995, Journal of the National Cancer Institute.

[2]  P. Delvenne,et al.  Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type. , 1995, American journal of clinical pathology.

[3]  C. Meijer,et al.  The presence of persistent high‐risk hpv genotypes in dysplastic cervical lesions is associated with progressive disease: Natural history up to 36 months , 1995, International journal of cancer.

[4]  S. Ménard,et al.  Expression of the monomeric 67-kd laminin-binding protein in human lymphomas as defined by MLuC5 monoclonal antibody and paraffin section immunohistochemistry. , 1995, Human pathology.

[5]  P. Delvenne,et al.  Inhibition of growth of normal and human papillomavirus-transformed keratinocytes in monolayer and organotypic cultures by interferon-gamma and tumor necrosis factor-alpha. , 1995, The American journal of pathology.

[6]  M. Fernö,et al.  Prognostic value of Ki‐67 expression in 182 soft tissue sarcomas. Proliferation — a marker of metastasis? , 1994, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[7]  S. Takasawa,et al.  Structural determination and characterization of a 40 kDa protein isolated from rat 40 S ribosomal subunit , 1994, FEBS letters.

[8]  P. Delvenne,et al.  Detection of human papillomaviruses in paraffin-embedded biopsies of cervical intraepithelial lesions: analysis by immunohistochemistry, in situ hybridization, and the polymerase chain reaction. , 1994, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[9]  W. Frable,et al.  Distribution of human papillomavirus types in genital lesions from two temporally distinct populations determined by in situ hybridization. , 1993, Human pathology.

[10]  S. Ménard,et al.  Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas. , 1993, Journal of the National Cancer Institute.

[11]  P. Delvenne,et al.  Detection of human papillomavirus DNA in biopsy-proven cervical squamous intraepithelial lesions in pregnant women. , 1992, The Journal of reproductive medicine.

[12]  T. R. Broker,et al.  Expression of high-affinity laminin receptor mRNA correlates with cell proliferation rather than invasion in human papillomavirus-associated cervical neoplasms. , 1992, Cancer research.

[13]  R Reid,et al.  Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. , 1992, Obstetrics and gynecology.

[14]  L. Liotta,et al.  Augmentation of type IV collagenase, laminin receptor, and Ki67 proliferation antigen associated with human colon, gastric, and breast carcinoma progression. , 1991, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[15]  G. Nuovo,et al.  Occurrence of multiple types of human papillomavirus in genital tract lesions. Analysis by in situ hybridization and the polymerase chain reaction. , 1991, The American journal of pathology.

[16]  G. Nuovo,et al.  In situ hybridization analysis of human papillomavirus DNA segregation patterns in lesions of the female genital tract. , 1990, Gynecologic oncology.

[17]  R. Richart A modified terminology for cervical intraepithelial neoplasia. , 1990, Obstetrics and gynecology.

[18]  L. Liotta,et al.  Evidence for a precursor of the high-affinity metastasis-associated murine laminin receptor. , 1989, Biochemistry.

[19]  D. Shibata,et al.  Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction , 1988, The Journal of experimental medicine.

[20]  R. Richart Causes and management of cervical intraepithelial neoplasia , 1987, Cancer.

[21]  G. Temple,et al.  Oncogenic association of specific human papillomavirus types with cervical neoplasia. , 1987, Journal of the National Cancer Institute.

[22]  H. Strander Interferon treatment of human neoplasia. , 1986, Advances in cancer research.

[23]  L. Liotta Tumor invasion and metastases--role of the extracellular matrix: Rhoads Memorial Award lecture. , 1986, Cancer research.

[24]  L. Liotta,et al.  Immunochemical and ultrastructural assessment of the nature of the pericellular basement membrane of human decidual cells. , 1985, Laboratory investigation; a journal of technical methods and pathology.

[25]  C. Crum,et al.  Human papillomavirus type 16 and early cervical neoplasia. , 1984, The New England journal of medicine.

[26]  M. Karnovsky,et al.  THF EARLY STAGES OF ABSORPTION OF INJECTED HORSERADISH PEROXIDASE IN THE PROXIMAL TUBULES OF MOUSE KIDNEY: ULTRASTRUCTURAL CYTOCHEMISTRY BY A NEW TECHNIQUE , 1966, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.