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IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis.

ABSTRACT: Expression of p16 has been established as a good surrogate marker for high-risk human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) patients, and it has been associated with an improved prognosis, irrespective of the actual HPV status. Conversely, the human insulin-like growth factor II mRNA binding protein 3 (IMP3) has been related to aggressiveness in several types of tumors. The aim of the present study was to investigate and compare p16 and IMP3 as markers of favorable and unfavorable behavior, respectively, in head and neck SCC (HNSCC), with particular reference to the HPV status. Both markers were analyzed by immunohistochemical analysis of 156 HNSCC samples originating from the oropharynx (n=81), oral cavity (n=44), larynx (n=15), hypopharynx (n=10) and nasopharynx (n=6). The HPV status was examined in a randomly selected representative subcohort (n=38) using polymerase chain reaction. Of the 156 HNSCC samples, 81 (51.9%) and 54 (34.6%) were positive for IMP3 and p16, respectively. IMP3 expression (P=0.022), p16 expression (P<0.001) and the combination of these markers (P<0.001) were significantly associated with tumor site. In particular, 69/81 (85%) OPSCC samples were positive for either one or both markers compared with 36/75 (48%) SCC samples from other sites. p16 expression was significantly associated with HPV infection (P=0.017) and a trend towards a negative association between IMP3 expression and HPV infection was observed (P=0.053). The results of the present study suggested that IMP3 and p16 are more frequently expressed in OPSCC compared with other HNSCCs. The prognostic impact of IMP3 on OPSCC remains to be investigated in a larger series with an extended follow-up period.

SUBMITTER: Riener MO

PROVIDER: S-EPMC5529926 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Oral squamous cell carcinoma (OSCC) is most common oral cancer with multifactorial etiology. Surgical therapy is treatment of choice but known to have recurrence. The main reason for recurrence is associated with surgical margins which need to be tumor free. Changes at genetic level cannot be ascertained only through routine light microscopy in surgical margins, even though they are tumor free. Detection of early marker like p16 can help in predicting the risk of recurrence. Hence study aimed to detect p16 microsatellite marker (D9s1747) in surgical margins of oral squamous cell carcinoma and compare the same with p16 marker through immunohistochemistry. Total of 40 paraffin embedded tissue samples diagnosed and surgically treated cases of OSCC were included. From each sample one tumor proper and one surgical margin was obtained. From paraffin embedded tissue sample 2 sections of 4 µm thick was obtained from tumor proper and tumor margin. One section was stained with hematoxylin and eosin and other section was stained immunohistochemically using p16 antibody. DNA extraction was done for tumor proper and surgical margin tissue and PCR analysis was carried for p16 microsatellite marker (D91747). Out of 40 cases 37 cases showed positivity in tumor proper for p16 with IHC. Out of 37 cases 23 cases showed positivity for both tumor proper and surgical margin. There were 3 cases negative for tumor proper. Out of these 3 cases, 1 (33.3%) case was positive for surgical margin. Out of 40 cases 27 cases showed positivity for tumor proper with p16 microsatellite marker. Out of 27 cases 16 cases showed positivity for both tumor proper and surgical margin. There were 13 cases negative for tumor proper. However there were 8 (61.5%) cases negative which were in tumor proper but showed positivity for surgical margin. Other 5 cases were negative in both tumor proper and surgical margin. Our study reveals that surgical margins of OSCC exhibit alteration in p16 markers both by IHC and PCR techniques. p16 and p16 microsatellite marker detection in margins indicates field change. Further studies with larger sample size comparing expression with clinical and histological parameter and follow up has to be done to substantiate our findings.

Project description:AbstractMicroRNAs (miRNAs) play critical roles in carcinogenesis and development of cancers. In this study, we analyzed the eccentrically expressed miRNAs in head and neck squamous cell carcinoma (HNSCC) tissues based on the miRNA-Seq data of HNSCC patients available in the Cancer Genome Atlas database. Aberrant expression of 2589 miRNAs was detected in HNSCC tissues (1128 downregulated and 1461 upregulated). The differential expression levels of the miRNAs were further validated by analysis of 25 HNSCC samples and paired control tissues and compared with the Gene Expression Omnibus database to determine the candidate miRNAs. Quantitative reverse transcription polymerase chain reaction was used to compare the expression of these candidate miRNAs between 22 fresh HNSCC tissue samples and 11 control samples. In addition, the relationship between the expression of these candidate miRNAs and Tumor, Node, Metastases staging of HNSCC was analyzed. Compared with the expression in control tissues, the levels of hsa-miR-410-3p, hsa-miR-411-5p, hsa-miR-125b-2-3p, and hsa-miR-99a-3p were significantly lower in HNSCC. According to the Cancer Genome Atlas dataset analyzed, all 4 miRNAs were shown to inhibit tumor progression (T stage), positive lymph node metastasis (N stage), and distant metastasis (M stage) in HNSCC. Kyoto Encyclopedia of Genes and Genomes analysis showed that genes regulated by these 4 miRNAs were enriched in certain pathways, including the transforming growth factor-β signaling pathway and the Hippo pathway. Enriched gene ontology terms mainly included regulation of transcription, cell proliferation, and apoptosis, which are well-characterized functions of miRNAs. Moreover, all 4 miRNAs inhibited the progression of primary tumors (T stage) and metastasis of regional lymph nodes (N stage). The top 4 aberrantly expressed miRNAs identified in this study have great clinical value in developing strategies for early diagnosis and treatment of HNSCC. More intensive studies are required to elucidate the mechanism underlying the roles of these miRNAs in HNSCC.

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IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis.

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