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Background: Salivary Adenoid Cystic Carcinoma (ADCC), also known as “Wolf in Sheep's clothing,” is associated with poor prognosis. Regardless of the vigorous treatment, ADCC has been known to recur and metastasize. Hence, identifying informative prognostic biomarkers for Salivary ADCC is of great importance to better predict tumor behavior and to guide treatment planning. Various immunohistochemical biomarkers along with other factors like the histologic grade of the tumor, site of tumor, and age have been studied to establish their correlation with the prognosis of ADCC. Aim: The aim of the systematic review was to identify various markers that have the potential to predict the prognosis in salivary ADCC. Materials and Methods: A literature search was conducted using PubMed and Scopus as database and Google Scholar as an additional source. Studies that performed immunohistochemical analysis predicting the overall survival of patients with salivary ADCC were included in this review. Studies published from 1977 to August 2018 were included. Case reports, review, letter to editors, and articles in languages other than English were excluded from the review. The following outcomes were examined: overall/disease-free survival, metastasis, and recurrence using immunohistochemistry as a prognostic marker. Results: A number of biomarkers were identified by the evaluation of 68 studies, which predicted overall survival and prognosis in terms of recurrence and metastasis. Out of these biomarkers, four markers most frequently assessed markers were Ki-67, p53, vascular endothelial growth factor (VEGF), and cyclin D1, which showed reproducible results. Many other markers showed significant results, but since only a single study was carried out with these markers, it was difficult to assess their predictability. Conclusion: The review thus identified that Ki-67, p53, VEGF could effectively predict metastasis and recurrence in salivary ADCC. More research work is, however, required to validate the accuracy of these markers for their prognostic significance. Many other markers also showed a significant correlation to prognosis; however, multiple studies are required to establish their prognostic value.
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