Tissue P16 is Associated with Smoking Status among Indonesian Nasopharyngeal Carcinoma Subjects

Wahyuningsih, Laila; Dwianingsih, Ery Kus; Risanti, Erika Diana; Tirtoprodjo, Prijono; Rinonce, Hanggoro Tri; Hakim, Fikar Arsyad; Herdini, Camelia; Fachiroh, Jajah

doi:10.31557/apjcp.2019.20.7.2125

Cited by 9 publications

(7 citation statements)

References 29 publications

(19 reference statements)

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“…The histological findings of our study resembles that of endemic areas worldwide, with a predominance of NK NPC, especially that of undifferentiated type which accounts for 85.9%. The findings in the present study can be paralleled with a study conducted in North Africa, an endemic region, where almost all (92%) cases were undifferentiated carcinomas (UCNT) and in Indonesia which is estimated to have an intermediate incidence of NPC, is also characterized with majority of NK NPC type [ 22 ].…”

Section: Discussionsupporting

confidence: 83%

Descriptive epidemiology of nasopharyngeal carcinoma at Tikur Anbessa Hospital, Ethiopia

et al. 2021

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Background Nasopharyngeal cancer is distinguished from other cancers of the head and neck in its epidemiology, histopathology, clinical characteristics, and therapeutic outcome. Its unique clinico-epidemiologic pattern of the disease is an area focus for this investigation. Accordingly, the study investigated the demographic and histologic characteristics, as well as the clinical stage at presentation of nasopharyngeal carcinoma patients at Tikur Anbessa Specialized hospital. Methods Hospital based retrospective descriptive study was conducted from September 2017 – October 2020. All biopsy proven incidental cases during the study period are included. SPSS version 26 is used for data entry and analysis. Result A total of 318 patients with histologically confirmed nasopharyngeal carcinoma cases during the study period were included. There were 218 males and 90 females, with a male: female ratio of 2.5:1. The age of patients ranges from 13 to 81 years with a mean age of 37.8 ± 15 years. The median age at diagnosis was 38 years. Age distribution has two peaks for males, first between 30 to 39 and second 50 to 59 years of age. While the peak age of occurrence for females is in the 20–39 age range. Juvenile cases constituted 34% of the study group. The study revealed, nonkeratinizing carcinoma as the most prevalent histology at 94.3% (undifferentiated type 85.9% and differentiated keratinizing squamous cell carcinoma 8.4%) and 5.7% of the cases showed keratinizing squamous cell carcinoma. Majority of the patients, 86%, presented late with stage III and IV disease. Conclusion Nasopharyngeal cancer is commonly found among the young and productive age group, under the age 30. Nonkeratinizing carcinoma is the predominant histopathologic variant resembling that seen in endemic areas of the world. Thus, genetic and early life environmental exposures should be well studied to identify possible risk factors in the region. Late-stage presentation at diagnosis impacts the treatment outcome of patients, thereby indicating the need for a raised index of suspicion among health professionals for early diagnosis and better prognosis of patients.

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Section: Discussionsupporting

confidence: 83%

Descriptive epidemiology of nasopharyngeal carcinoma at Tikur Anbessa Hospital, Ethiopia

et al. 2021

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“…Previous reports have described the occurrence of p53 mutations and CDKN2A ( p16 ) deletions in ATLL [ 28 , 29 , 30 , 31 , 32 ]. Inactivation of p16 has been found in nearly 50% of all human cancers, caused by deletion, methylation, or gene mutations, leading to alterations in protein production [ 14 ]. Since the frequency of p16 deletion is reported to increase as the ATLL stage progresses [ 28 ], we expected that patients with ATLL might have lower scores for p16 expression in our immunostaining analyses compared to those with PTCL-NOS.…”

Section: Discussionmentioning

confidence: 99%

“…The human CDKN2A gene encodes a tumor suppressor protein known as p16. This cyclin-dependent kinase inhibitor regulates the G1 phase of the cell cycle and it is frequently inactivated in cancer [ 14 ]. In contrast, SOX4 is frequently overexpressed in a variety of solid tumors, where it functions as an oncogene [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma

et al. 2021

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Differentiation between adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is often challenging based on pathological findings alone. Although serum anti-HTLV-1 antibody positivity is required for ATLL diagnosis, this information is often not available at the time of pathological diagnosis. Therefore, we examined whether the expression of SOX4 and p16 would be helpful for differentiating the two disease entities. We immunohistochemically examined SOX4 and p16 expression (which have been implicated in ATLL carcinogenesis) in 11 ATLL patients and 20 PTCL-NOS patients and classified them into four stages according to the percentage of positive cells. Among the ATLL cases, 8/11 (73%) were SOX4-positive, while only 2/20 (10%) PTCL-NOS cases expressed SOX4. The mean total score was 4.2 (standard deviation (SD): 0.61) in the ATLL group and 0.50 (SD: 0.46) in the PTCL-NOS group (p < 0.001). Positive expression of p16 was noted in 4/11 (36%) patients with ATLL and 3/20 (15%) patients with PTCL-NOS, with mean total scores of 1.9 (SD: 0.64) and 0.70 (SD: 0.48) in the ATLL and PTCL-NOS groups, respectively (p = 0.141). These results suggest that SOX4 may be strongly expressed in ATLL compared to PTCL-NOS cases. Therefore, it may be helpful to perform immunohistochemical staining of SOX4 when pathologists face challenges discriminating between ATLL and PTCL-NOS.

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“…In another study conducted in Ishikawa, Japan, the endometrial adenocarcinoma cells of the participants were treated with components of tobacco [ 23 ]. An association was found between TSU and the downregulation of the P16 tumor suppressor protein encoded by the CDKN2A gene that slows down cell division [ 24 ]. In addition, a reduction in expression was found to occur in the pathways of the cyclin-dependent kinase inhibitors P21 and P27, with their expression increasing inside the levels of transmission of the cyclins D1 and E. Moreover, previous studies have demonstrated the significant association between TSU and mutations in P53, which cause squamous cell carcinoma in the lungs.…”

Section: Introductionmentioning

confidence: 99%

Association between tobacco substance usage and a missense mutation in the tumor suppressor gene P53 in the Saudi Arabian population

Almutairi

Alrubie

et al. 2021

PLoS ONE

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The tumor suppressor gene TP53 and its downstream genes P21 and MDM2 play crucial roles in combating DNA damage at the G1/S cell cycle checkpoint. Polymorphisms in these genes can lead to the development of various diseases. This study was conducted to examine a potential association between tobacco substance usage (TSU) and single-nucleotide polymorphism (SNP) at the exon regions of the P53, P21, and MDM2 genes by comparing populations of smokers and non-smokers from Saudi Arabia. P53 rs1042522 (C/G), P21 rs1801270 (A/C), and MDM2 rs769412 (A/G) were investigated by genotyping 568 blood specimens: 283 from male/female smokers and 285 from male/female non-smokers. The results obtained from the smokers and their control non-smokers were compared according to age, sex, duration of smoking, and type of TSU. Heterozygous CG, homozygous GG, and CG+GG genotypes, as well as the G allele of rs1042522 were significantly associated with TSU in Saudi smokers compared with non-smokers. The C allele frequency of rs1801270 was also associated with TSU in smokers (OR = 1.33, p = 0.049) in comparison with non-smokers, in younger smokers (≤29 years) (OR = 1.556, p = 0.03280) in comparison with non-smokers of the same age, in smokers who had smoked cigarettes for seven years or less (OR = 1.596, p = 0.00882), and in smokers who had consumed shisha (OR = 1.608, p = 0.04104) in comparison with the controls. However, the genotypic and allelic frequencies for rs769412 did not show significant associations with TSU in Saudis. The selected SNP of P53 was strongly associated with TSU and may be linked to TSU-induced diseases in the Saudi Arabian population.

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Tissue P16 is Associated with Smoking Status among Indonesian Nasopharyngeal Carcinoma Subjects

Cited by 9 publications

References 29 publications

Descriptive epidemiology of nasopharyngeal carcinoma at Tikur Anbessa Hospital, Ethiopia

Descriptive epidemiology of nasopharyngeal carcinoma at Tikur Anbessa Hospital, Ethiopia

Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma

Association between tobacco substance usage and a missense mutation in the tumor suppressor gene P53 in the Saudi Arabian population

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