Effects of Mycophenolate Mofetil, Methotrexate and Pimecrolimus on cdk4 and p16 in Erosive Oral Lichen Planus.

BACKGROUND: This study evaluated the effect of mycophenolate mofetil, methotrexate, and pimecrolimus on the expression of cdk4 and p16, important proteins implicated in hyperproliferation and arrest in the G1 phase, in oral lichen planus (OLP). MATERIALS AND METHODS: In this randomized clinical trial, 60 patients were randomly assigned in three equal groups to receive either pimecrolimus cream, or mycophenolate mofetil or methotrexate, both supplemented with pimecrolimus. Pretreatment and post-treatment specimens were immunohistochemically stained for detecting cdk4 and p16. RESULTS: A significant decrease in cdk4 cytoplasmic positivity was noted in all three treatment groups and was especially more significant in the MTX group (P < 0.0001) than in the other two groups (P < .001). However, a significant decrease in the cdk4 nuclear staining was noted with only systemic treatment groups of MMF (P < 0.05) and MTX (P < 0.01), both supplemented with pimecrolimus. No significant decrease in cytoplasmic p16 levels was noted in the MTX group while a significant decrease in cytoplasmic p16 levels was noted in the other two groups; however, no significant decrease in p16 nuclear staining was noted with any treatment. CONCLUSION: By decreasing the expression of cdk4 and p16, pimecrolimus, methotrexate, and mycophenolate mofetil decrease the malignant potential of OLP lesions. However, methorexate can be a better alternative in cases showing high cdk4 expression.

Role of serum interleukin-6 in deciding therapy for multidrug resistant oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell mediated immune response. T cells locally present in the involved tissues release cytokines like interleukin-6 (IL-6), which contributes to pathogenesis of OLP. Also IL-6 has been associated with multidrug resistance protein (MRP) expression by keratinocytes. Correspondingly, upregulation of MRP was found in OLP. We conducted this study to evaluate the effects of various drugs on serum IL-6 in OLP; and correlation of these effects with the nature of clinical response and resistance pattern seen in OLP lesions with various therapeutic modalities. Thus we evaluated the role of serum IL-6 in deciding therapy for multidrug resistant OLP. MATERIAL AND METHODS: Serum IL-6 was evaluated in 42 erosive OLP (EOLP) patients and 10 normal mucosa and 10 oral squamous cell carcinoma cases using ELISA technique. OLP patients were randomly divided into 3 groups of 14 patients each and were subjected to Pimecrolimus local application, oral Mycophenolate Mofetil (MMF) and Methotrexate (MTX) alongwith Pimecrolimus local application. IL-6 levels were evaluated before and after treatment. RESULTS: Serum IL-6 levels were raised above 3pg/ml in 26.19% erosive OLP (EOLP) cases (mean- 3.72±8.14). EOLP (5%) cases with IL-6 levels above 5pg/ml were resistant in MTX group. However significant decrease in serum IL-6 corresponding with the clinical resolution was seen in MMF group. CONCLUSIONS: Significantly raised IL-6 levels in EOLP reflect the chronic inflammatory nature of the disease. As serum IL-6 levels significantly decreased in MMF group, correspondingly no resistance to treatment was noted. However with MTX there was no significant decrease in IL-6 and resistance to treatment was noted in some, especially plaque type lesions. Thus IL-6 can be a possible biomarker in deciding the best possible therapy for treatment resistant OLP. KEY WORDS: Lichen planus, biological markers, cytokines, enzyme-linked immunosorbent assay, immunosuppressive agents.

Expression of cdk4 and p16 in Oral Lichen Planus.

OBJECTIVES: The purpose of this study was to evaluate the expression of cdk4 and p16, the proteins implicated in hyperproliferation and arrest in oral lichen planus and to compare their expression in erosive and non-erosive oral lichen planus and with normal mucosa and oral squamous cell carcinoma. MATERIAL AND METHODS: Analysis of cdk4 and p16 expression was done in 43 erosive oral lichen planus (EOLP) and 17 non-erosive oral lichen planus (NOLP) cases, 10 normal mucosa and 10 oral squamous cell carcinoma (OSCC) cases with immunohistochemistry. RESULTS: This study demonstrated a significantly increased expression of cytoplasmic cdk4 (80% cases, cells stained - 19.6%), and cytoplasmic p16 (68.3% cases, cells stained - 16.4%) in oral lichen planus (OLP) compared to normal mucosa. cdk4 was much higher in OSCC in both cytoplasm and nuclei compared to normal mucosa. Also, while comparing OLP with positive control, significant difference was noted for cdk4 and p16, with expression being more in OSCC. While comparing EOLP with NOLP; significant differences were seen for cdk4 cytoplasmic staining only, for number of cases with positive staining as well as number of cells stained. CONCLUSIONS: Overexpression of cytoplasmic cdk4 and p16 was registered in oral lichen planus, however considerably lower than in squamous cell carcinoma. Erosive oral lichen planus demonstrated overexpression of cytoplasmic cdk4 and premalignant nature compared to non-erosive lesion. Therefore there is an obvious possibility for cytoplasmic expression of cdk4 and p16 to predict malignant potential of oral lichen planus lesions.

The current approach to the diagnosis of vascular anomalies of the head and neck: A pictorial essay.

Throughout the years, various classifications have evolved for the diagnosis of vascular anomalies. However, it remains difficult to classify a number of such lesions. Because all hemangiomas were previously considered to involute, if a lesion with imaging and clinical characteristics of hemangioma does not involute, then there is no subclass in which to classify such a lesion, as reported in one of our cases. The recent classification proposed by the International Society for the Study of Vascular Anomalies (ISSVA, 2014) has solved this problem by including non-involuting and partially involuting hemangioma in the classification. We present here five cases of vascular anomalies and discuss their diagnosis in accordance with the ISSVA (2014) classification. A non-involuting lesion should not always be diagnosed as a vascular malformation. A non-involuting lesion can be either a hemangioma or a vascular malformation depending upon its clinicopathologic and imaging characteristics.