Sialoblastoma: Utility of Ki-67 and p53 as a Prognostic Tool and Review of Literature

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Pediatric and Developmental Pathology (Impact Factor: 0.87). 12/2009; 13(1):32-8. DOI: 10.2350/09-05-0650-OA.1
Source: PubMed


Sialoblastoma is a rare tumor of the salivary gland that commonly occurs in the parotid gland and occasionally in the sub-mandibular gland. The malignant potential of sialoblastoma has been documented in only 3 of 32 cases of sialoblastoma reported thus far. In the last 15 years, we have encountered 2 cases of sialoblastoma, in a newborn and in a 15-year-old boy, both arising within the parotid gland. Case 1 has been previously reported and although there were 2 recurrences, at 1 and 9 years post resection, it has shown benign biological behavior. Case 2 is unusual since the patient presented with metastases. We reviewed the 2 cases, including the 2 recurrences from the first case, for histologic and immunohistochemical differences. Although both cases showed similar cytomorphologic features, there was a significant difference in Ki-67 expression: 20% in case 1 (original tumor), <2% in case 1 (recurrent tumor), and nearly 70-80% in the recent malignant case. The difference is remarkable when combined with p53 expression, which was focally positive in the first case but diffusely positive in the second. This report highlights the potential utility of proliferation markers such as Ki-67 in concert with p53 expression to better predict the biological behavior of a rare but locally aggressive neoplasm.

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    • "Ki-67 is a nuclear protein attaching to nuclear antigens expressed in phases of the proliferation except G0, and it serves as one of the major factors related to tumor proliferation, which can be assessed by Ki-67 or MIB-1 antibody with immunohistochemistry (IHC) [6] [7]. Besides, there have been already studies demonstrating that Ki-67 LI was strongly associated with the aggressiveness of tumor, including prostate cancer, astrocytomas, gastroentero-pancreatic neuroendocrine tumors, sialoblastoma, lung cancer, breast cancer and pituitary adenomas [8] [9] [10] [11] [12] [13] [14]. In addition, several meta-analyses conclude that high Ki-67 LI could predict poor prognosis in patients with cervical cancer, gliomas, lymphoma, breast cancer, and lung cancer [15- 19]. "
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    ABSTRACT: Background: The relationship between Ki-67 labeling index (LI) and clinical outcome in hepatocellular carcinoma (HCC) has been investigated by various studies, but no consistent result has been concluded. To define the prognostic significance of Ki-67 LI in patients with HCC, we performed a meta-analysis. Methods: We searched for literatures in the following databases: PubMed, ISI Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Science Direct, Wiley Online Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Chinese VIP and WanFang Databases. Our search ended on April 6th, 2015. Data were extracted from eligible studies and the correlation between Ki-67 LI and clinicopathological features of HCC was analyzed and pooled hazard ratios (HRs) for eligible studies were calculated by STATA 11.0 (STATA Corp., College, TX). Results: In total, 54 studies involving 4996 patients were included in the current meta-analysis. The meta-analysis provided evidence that high Ki-67 LI was closely associated with histological grade, tumor size, number of tumor nodes, the status of metastasis, cirrhosis and vein invasion in HCC patients. The pooled HRs showed that high Ki-67 LI had an unfavorable impact on disease-free survival (DFS) (HR=1.626, 95% confidence interval (CI): 1.364-1.939, P<0.001), relapse-free survival (RFS) (HR=1.820, 95% CI: 1.215-2.725, P=0.004) and overall survival (OS) (HR=1.170, 95% CI: 1.102-1.243, P<0.001), respectively. Additionally, subgroup analysis indicated that high Ki-67 LI was related to poorer DFS, RFS and OS independent of regions, treatment strategies or statistical methods, except that no statistical significance was found on RFS (HR=2.413, 95% CI: 0.523-11.142, P=0.259) and OS (HR=1.998, 95% CI: 0.797-5.009, P=0.14) in patients with liver transplantation. Conclusions: Our meta-analysis suggests that higher Ki-67 LI confers a fast progression and poor prognosis for HCC patients.
    International Journal of Clinical and Experimental Medicine 09/2015; 8(7):10235-47. · 1.28 Impact Factor
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    ABSTRACT: Interferon regulatory factor 1 (IRF1) shows tumor-suppressor activity by suppressing proliferation of cancer cells. To exert its anti-proliferative effects, this factor must ultimately control transcription of several key genes that regulate cell cycle progression. Here, we showed that Ki-67 gene is a novel proliferation-related downstream target of IRF1. IRF1 repressed Ki-67 gene transcription in a dose-dependent manner in human Ketr-3 and 786-O renal carcinoma cells. We previously cloned the Ki-67 core promoter which contained two functional Sp1 binding sites. Mutation of the two Sp1 binding sites abrogated Sp1-dependent enhancement of Ki-67 promoter activity. Forced elevation of IRF1 decreased endogenous Sp1 protein level. However, there was no effect on Sp1 mRNA level after transfected with IRF1. Our findings establish a casual series of events that connect anti-proliferative effects of IRF1 with the Ki-67 gene, which encodes a key regulator of the G1/S phase transition. It suggests that the inhibitory effect on Ki-67 gene expression mediated by decreasing level of Sp1 protein might be a novel function of the anti-tumor activity of IRF1.
    Tumor Biology 08/2012; 33(6). DOI:10.1007/s13277-012-0483-3 · 3.61 Impact Factor

  • Journal of the American Academy of Dermatology 12/2012; 67(6):e276-7. DOI:10.1016/j.jaad.2012.05.032 · 4.45 Impact Factor
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