Pathology
Assessment of Laminin-5 in Oral Dysplasia and Squamous Cell Carcinoma

https://doi.org/10.1016/j.joms.2013.04.032Get rights and content

Purpose

Laminin-5 is an important protein in the establishment of an intact basement membrane. The aims of this study were to assess the expression of laminin-5 (γ2 chain) using cyclin D1 and Ki-67 in hyperplastic oral mucosal lesions, oral dysplasia, and squamous cell carcinoma (SCC).

Materials and Methods

Paraffin-embedded tissue blocks of 134 patients were stained for laminin-5, cyclin D1, and Ki-67 using immunohistochemistry and assessed by virtual microscopy. Statistical analysis was performed using Kruskal-Wallis tests and Mann-Whitney U tests for post hoc assessment.

Results

Laminin-5, cyclin D1, and Ki-67 were found to have significant differences in expression for the different categories of dysplasia, SCC, and hyperplasia (P < .001). Cyclin D1 and Ki-67 expression levels were significantly increased in moderate and severe dysplasia and SCC, with no significant difference in expression between hyperplasia and mild dysplasia or between biopsies of severe dysplasia and SCC. Laminin-5 expression was only significantly increased in SCC, confirming it as a marker of malignant transformation and invasion.

Conclusions

The results of this study indicate that overexpression of laminin-5 is found only in SCC and not dysplastic lesions. Therefore, laminin-5 has potential as a marker for the intraoperative assessment of cancer excision margins and could be used as a target for chemotherapeutic agents.

Section snippets

Materials and Methods

Tissue blocks of patients with a confirmed diagnosis of mild, moderate, or severe dysplasia, SCC, and tissue hyperplasia of the oral mucosa were obtained from the Oral Pathology Diagnostic Service, Melbourne Dental School, University of Melbourne (Melbourne, Australia) from 1992 through 2009. Data collected included gender and date of birth, with the histologic diagnosis being confirmed by a review of the original slides stained with hematoxylin and eosin by an oral and maxillofacial

Results

One hundred thirty-six patients were included in the study (70 women, 51.5%; 66 men, 48.5%). The mean age of the patient group was 63.1 years (standard deviation, 13.6 yr; range, 30 to 87 yr). The pathologic diagnoses were epithelial hyperplasia in 24 patients (17.6%), mild dysplasia in 27 (19.9%), moderate dysplasia in 8 (5.9%), severe dysplasia in 29 (21.1%), and SCC in 48 (35.3%).

The immunohistochemical results showed significant variation in the mean and median pixel levels for hyperplasia,

Discussion

The present study found a significant increase in cytoplasmic laminin-5 expression in SCC with no significant increase in expression in dysplastic lesions. The expression of cycle markers cyclin D1 and Ki-67 significantly increased with increasing grade of dysplasia and SCC. This is in keeping with the idea that one of the main features of malignant transformation is increased and dysregulated cellular proliferation.

With regard to laminin-5, the findings of the present study add to previous

References (32)

  • A. Chandu et al.

    Factors affecting survival in patients with oral cancer: An Australian perspective

    Int J Oral Maxillofac Surg

    (2005)
  • A. Chandu et al.

    Health-related quality of life in oral cancer: a review

    J Oral Maxillofac Surg

    (2006)
  • I.R. Kramer et al.

    Definition of leukoplakia and related lesions: An aid to studies on oral precancer

    Oral Surg Oral Med Oral Pathol

    (1978)
  • S. Silverman et al.

    Oral leukoplakia and malignant transformation: A follow-up study of 257 patients

    Cancer

    (1984)
  • J. Lo et al.

    An immunohistochemical analysis of cell cycle marker in oral mucosal dysplastic lesions treated by laser therapy: A pilot study

    J Maxillofac Oral Surg

    (2011)
  • A. Bilde et al.

    Molecular markers in the surgical margin of oral carcinomas

    J Oral Pathol Med

    (2009)
  • Cited by (9)

    • Multiple roles for basement membrane proteins in cancer progression and EMT

      2022, European Journal of Cell Biology
      Citation Excerpt :

      Collagen IV protein is crucial for maintaining the structure and function of BMs under circumstances of upregulating mechanical demands but is replaceable for deposition and initial assembly of components. Laminin is sufficient for basement membrane-like matrices at early stages, but at later stages, collagen IV is responsible for stability, integrity, and functionality (Pöschl et al., 2004). Integrins help in adhesion, which is essential for regulating various biological functions of cancer cells and act as receptors of ECM, thereby mediating the interactions between cells-cells and cells-ECM.

    • Study on the expression and function of smad family member 7 in oral submucous fibrosis and oral squamous cell carcinoma

      2020, Archives of Oral Biology
      Citation Excerpt :

      Besides, López-Graniel et al. reported that the density of micro-vessel showed correlation with increasing T and N stages in OSCC (López-Graniel et al., 2001). Furthermore, laminin was found to be an important protein in the establishment of an intact basement membrane detecting by immunohistochemistry in paraffin-embedded tissue blocks of 134 patients conducted by Rani, McCullough, and Chandu (2013). The main feature is the destruction of the integrity of the basement membrane in the progress from OSCC in situ to invasive OSCC.

    • Laminins and cancer stem cells: Partners in crime?

      2017, Seminars in Cancer Biology
      Citation Excerpt :

      As a result, overexpression of laminin α4 had the possibility of serving as a marker for malignant and metastatic breast cancer cells and shown a positive correlation with increased recurrence rate of patients compared to those had lower levels [78]. Laminin γ2 chain was previously shown to be a molecular marker for cells with invasive properties and correlated with poor prognosis, suggesting a potential role in CSCs [24,25,27]. It has recently been confirmed both in vitro and in vivo that the γ2 chain, for example in laminin-332, has an elevated mRNA expression in the CSC population isolated by the side population technique.

    View all citing articles on Scopus
    View full text