6. brief resume of the inteded work 1 need for the study



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5. TITLE OF THE TOPIC

“STUDY OF EXPRESSION OF LAMININ-332 γ2 IN ORAL VERRUCOUS CARCINOMA : AN IMMUNOHISTOCHEMICAL STUDY”



6. BRIEF RESUME OF THE INTEDED WORK

6.1 NEED FOR THE STUDY

Oral verrucous carcinoma (OVC) is an extremely well differentiated and distinct variant of oral squamous cell carcinoma (OSCC) . Also, OVC is a phenomenon with slow growth, no metastatic potential, and lowest invasive potential. This variant of OSCC has unique biological behaviour and is fairly rare compared with the conventional form of OSCC . In contrast OSCC is the most common oral cancer, and also has regional lymph node involvement and distant metastatic potential. The oral cavity is one of the predilection sites for verrucous carcinoma. Tobacco chewing is a significant etiologic factor for development of OVC. Lesions often develop at the site where the tobacco was placed habitually. Recently, the role of human papilloma virus and over expression of p53 oncogene seems to be a significant etiological factor for verrucous carcinoma. In India, approximately 7% of oral cancers are verrucous carcinomas.

The histopathology of OSCC consistently show the invasion into the underlying connective tissue . This finding is supported by numerous studies which shows discontinuous expression of basement membrane protein Laminin. Although OVC is not reported to show invasion into underlying connective tissue, they are known to transform into OSCC, if left untreated. The possibility of breakdown of Laminin much prior to the gross appearance of break in the basement membrane cannot be ruled out. Timely detection of these molecular changes which can eventually lead to invasion can reduce the diagnostic dilemma among pathologist and clinician regarding the possible transformation into malignancy.

As invasion and metastases are the hallmark features of malignancy, evaluation of Laminin expression in OVC, may explain the unique biological behaviour of this lesion.There are very few studies, especially from developing countries such as India on verrucous carcinoma. Hence the present study is taken up to assess expression of Laminin-332 γ2 in OVC and to describe their possible role in pathogenesis and unique behaviour of the lesion.



6.2 REVIEW OF LITERATURE

Massoumeh zargaran et al studied the type IV collagen and laminin-332 γ2 chain expression in well differentiated squamous cell carcinoma and oral verrucous carcinoma, and suggested that, evaluation of Laminin-332 γ2 chain expression may be useful as a marker for description of biological behaviour and diagnosis of OVC from well differentiated OSCC, especially in doubtful cases.

Polo G. Arduino et al investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in verrucous carcinoma, severe epithelial dysplasia(SED) and SCC in order to analyse if the pattern of expression of these molecules contributes to the differences in the biological behaviour of these diseases. Their study indicated that VC had a biological behaviour different from SED or SCC, as observed by the immunohistochemistry in basement membrane zone.

A. Gasparoni, et al compared the expression of the subunit γ2 of Laminin-5 under normal, dysplastic and invading epithelia in 65 biopsies previously diagnosed for OSCC, and showed that γ2 may be a reliable prognostic tool for OSCC.

Yukki Ono, Yukhiro Nakanishi et al studied the Laminin-5 γ2 expression in OSCC of tongue in 67 patients and concluded that increased Laminin-5 γ2 chain immunoreactivity may reflect a high invasive potential of cancer cells and is a factor indicative of poor prognosis.

Yuchiro Kuratomi, Mayuko Kumamato et al analysed expression of Laminin γ2 chain in the primary lesions of 20 patients with advanced tongue cancer and showed that diffuse expression of Laminin γ2 might indicate a highly malignant state in advanced tongue cancer.



6.3 OBJECTIVE OF THE STUDY

  • To study the immunohistochemical expression of Laminin-332 γ2 in oral verrucous carcinoma.

  • To correlate with the histopathological features.



7. MATERIAL AND METHODS

7.1 SOURCE OF DATA

Samples represent the patients attending the out-patient department of P.M.N.M

DENTAL COLLEGE AND HOSPITAL, BAGALKOT, S. N. MEDICAL COLLEGE

AND SRI HANAGAL KUMARESHWARA HOSPITAL AND RESEARCH CENTRE

and references from various peripheral centres.

7.2 METHOD OF COLLECTION OF DATA

This study includes retrospectively and prospectively obtained 15 cases of oral

Verrucous carcinoma and 5 cases of oral squamous cell carcinoma. Based on H &E histopathological diagnosis of oral verrucous carcinoma, unstained section will be subjected for immunohistochemical evaluation of Laminin-332 γ2 expression with appropriate methods.

Immunohistochemical expression of Laminin-332 γ2 evaluated by two experienced oral

Pathologists. Obtained results will be analyzed statistically using appropriate methods

by biostatistician.


Inclusion criteria

Histologically diagnosed cases of oral verrucous carcinoma without foci of OSCC.


7.3. DOES YOUR STUDY REQUIRE ANY INVESTIGATION INTERVENTION TO BE CONDUCTED ON PATIENT OR OTHER HUMAN OR ANIMAL?

NO
7.4. HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION



IN CASE OF 7.3?

YES


8.LIST OF REFERENCES

1. Massoumeh Zargaran et al. Immunohistochemical evaluation of type IV collagen and Laminin-332 γ2 chain expression in well differentiated oral squamous cell carcinoma and oral verrucous carcinoma: a recommended cut off. JOPM 2011;40:167-173.

2. Polo G. Arduino et al. Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of oral mucosa. Clinical Oral Investigation 2010; 14:297-302.

3. A .Gasparoni et al. Prognostic value of differential expression of Laminin-5 γ2 in oral squamous cell carcinoma: Correlation with survival. oncology Reports 2007; 18: 793-800.

4. Yukki ono, Yukihiro Nakanishi et al. Clinicopathological Significance of Laminin 5γ2 Chain Expression in Squamous Cell Carcinoma of the Tongue. American Cancer Society 1999; 2315-2321.

5. Yuchiro Kuratomi, Mayuko Kumamato et al. Diffuse expression of laminin γ2 chain in disseminating and infiltrating cancer cells indicates a highly malignant state in advanced tongue cancer. Oral Oncology 2006; 42: 73-76.



6. Madhu verma , Jeevan lata. Verrucous carcinoma- an enigmatic entity. Indian Journal of Dentistry 2011; 33-36.

7. Rohan R walvekar et al. Verrucous carcinoma of oral cavity: A clinical and pathological study of 101 cases. Oral Oncology 2009; 45: 47-5.
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