Assessment of lymph vessel density (LVD) and lympho-vascular invasion (LVI) in squamous cell carcinoma (SCC) of the penis using D2-40 and p53 immunostaining and correlation of these markers with lymph node metastasis

Miriam, M Bidari (2016) Assessment of lymph vessel density (LVD) and lympho-vascular invasion (LVI) in squamous cell carcinoma (SCC) of the penis using D2-40 and p53 immunostaining and correlation of these markers with lymph node metastasis. Masters thesis, Christian Medical College, Vellore.


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INTRODUCTION: Squamous cell carcinoma of the penis is an uncommon tumor in the affluent developed countries (age standardized incidence rate 0.3-1/100,000 according to WHO). However, in developing countries like India, it is very common and the incidence is similar to that of cervical cancer. It accounts for about 0.4%-0.6% of all tumors in males in USA and Europe, and is about 20% of all malignancies in Asian countries. This depicts that environmental factors play a major role. According to the Western literature, the mean age at presentation is 60 years; however, in areas of high incidence, penile carcinoma presents at an earlier age. In India, the age of presentation can be as low as 35 years. Penile cancers with involvement of lymph nodes have a poor prognosis. Indeed the prognosis of carcinoma of penis depends upon an accurate diagnosis of the lymph node status. Involvement of the lymph node is the most important predictor of outcome for survival in penile carcinoma. However clinical estimation of the lymph node status in these patients is still a major problem, since 20-25% of clinically node negative patients can have occult nodal metastasis. On the other hand, traditional elective lymphadenectomy accounts for overtreatment in up to 80% of patients and is associated with high morbidity (30-90%). OBJECTIVES: 1. To detect early metastasis in amputed specimens of penis, by using two immuno markers, D2-40 and p53 and correlation of these with the histopathological variables and clinical stage 2. Also to compare which marker is the better predictor for metastasis. METHODS: Study was retrospective of total 49 cases of partial /total amputation with lymphadenectomy of penile cancers diagnosed between January 2006 to september 2014 in the Department of General pathology; Christian medical college and hospital were retrieved. These 49 cases were divided into metastatic and non metastatic groups on H&E sections in which 16/49 had metastasis. Two immunomarkers D2-40 and p53 were done on the amputed specimens to predict early metastasis. The p53 tumor density was calculated in 100 cells with 20% cut off and was graded as positive when more than 20% of the tumor cells with positive nuclear staining. For D2-40, LVD was calculated in the peritumoral and normal area by taking 10 % cutoff of positive staining of lymphatic cells within the lymphatics. All the pathological and clinical variables were calculated by Chi square test. In our study only the histopathological stage of the tumor statistically correlated with the p53 tumor marker. D2-40 did not show any correlation statistically with any pathological or clinical variable. RESULTS: Total 49 cases of partial amputed specimens had conventional SCCs and most common grade was grade I and common site of presentation was glans with mean depth of 0.9mm. Total 16 cases had lymph node metastasis, 17 /49 had LVI. Most common histopathological stage was T2 and most of our patients were clinically N0 status. Most common node involved was right superficial inguinal lymph node. 13 /49 cases with increased p53 tumor density and 11/49 showed increased LVD by D2-40 in 16 metastatic nodes and 23 in 33 nonmetastatic nodes. P value of 0.05 was considerd significant in our study. P53 had a sensitivity of (81.3%) and specificity of (54.4%) with positive predictive value of (36.1%)(CI20.8%-53.8%) and negative predictive value of (76.9%) (CI 46.2%- 95.0%). D2-40 had (68.8%) sensitivity and (42.4%) specificity with positive predictive value of (36.7%)(CI 19.9%-56.1%) and negative predictive value of (73.7%)(CI 48.8%-90.9%). Both the markers did not correlate statistically with histopathological and clinical variables like phimosis, BXO, clinical node status, tumor type, tumor grade, depth of invasion, LVI. Both had low positive predictive value. Therefore in our study p53 and D2-40 cannot predict the early lymph node metastasis because of low positive predictive value, even though they are sensitive. To conclude, both the markers had low specificity and low positive predictive value, which suggest that they are not able to predict lymph node metastasis even though they are sensitive and therefore they are not helpful to decide for prophylactic lymphadenectomy. D2-40 can be used as a good adjunct along with H& E sections on the initial amputated specimens to detect the definite LVI which needs to be confirmed by D2-40 staining in difficult and doubtful situations, on routine histology.

Item Type: Thesis (Masters)
Uncontrolled Keywords: SCC ; Lymphatic vessel density (LVD) ; Lymphovascular invasion (LVI) ; D2-40 and p53.
Subjects: MEDICAL > Pathology
Depositing User: Punitha K
Date Deposited: 13 Jun 2018 01:59
Last Modified: 13 Jun 2018 01:59

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