Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.     

口咽鳞状细胞癌患者预后影响因素分析

目的探讨口咽鳞状细胞癌患者的预后现状和影响因素。方法采用自制问卷收集2005年12月—2009年12月作者所在医院收治的69例口咽鳞状细胞癌患者的临床资料,根据口咽鳞状细胞癌患者的预后情况将其分为A组和B组。采用SPSS 19.0统计软件进行描述性统计和二分类Logistic回归分析口咽鳞状细胞癌预后现状和影响因素。结果所有患者中,死亡患者42例,预后不良患者比例为60.87%;人乳头瘤病毒感染(OR=12.167)、淋巴结转移(OR=24.184)、情绪紧张(OR=8.576)、治疗并发症(OR=11.470)和基础疾病种数多(OR=12.198)是口咽鳞状细胞癌患者预后不良的危险因素;肿瘤组织分化程度高(OR=0.118)是口咽鳞状细胞癌患者预后良好的保护因素。结论口咽鳞状细胞癌患者预后较差,预后结局受多方面因素影响,治疗中应采取针对性的预防干预措施来提高疗效,改善患者的预后。     

p16抑癌基因产物在原发性肝细胞癌中的表达及临床意义

目的分析p16蛋白测定在肝癌临床中的地位,并推测p16基因在肝细胞癌发生发展过程中的作用.方法采用免疫组化SP法测定34例原发性肝细胞癌、20例癌旁肝细胞中p16蛋白表达,分析与肝细胞癌组织学分级、TNM分期、生存预后等关系.结果64.7%的原发性肝细胞癌p16蛋白表达阳性,35.3%阴性,癌旁肝组织表达100%阳性.两者差异显著(P＜0.05).组织学分化Ⅳ级的肝细胞癌表达阳性率为41.7%、Ⅰ～Ⅲ级分化的阳性率75%～77.8%,对比有差异显著性(P＜0.05).TNM Ⅰ～Ⅳ期各组间p16蛋白的表达无差异.术后1、3年生存率在p16蛋白阳性者分别为93.7%和72.7%,阴性者分别为77.8%和60%.结论部分肝细胞癌组织存在p16蛋白的表达缺失现象.p16蛋白表达障碍可能与肝细胞癌的发生和组织分化有关.p16蛋白是否可作为本病恶性行为判断、预后分析的参考指标值得进一步研究.     

~(18)F-FDG PET显像在诊断消化道良恶性肿瘤和术后随访中的应用价值

目的 通过18F-FDG PET显像在消化道良恶性肿瘤鉴别诊断和随访结果,与CT/MR和手术病理结果的对比研究,以评价PET在消化道肿瘤中的临床应用价值。方法 消化道恶性肿块13例(胰腺癌10例,直肠癌2例和肝癌1例)、良性肿块5例和恶性肿瘤(胃癌5例,直肠癌4例和肝癌1例)手术治疗后10例共28例患者进行~(18)F-FDG PET全身显像,采用双盲法将PET诊断结果与同期的CT/MR影像结果进行比较。结果 13例消化道恶性肿块PET和CT/MR均见原发灶病变,10例PET显像结果与CT/MR相同,另外3例胰腺癌患者PET显像见腹腔淋巴结和脊柱转移。5例良性消化道占位性病变PET全身显像均阴性,其中1例病例病理诊断为直肠腺瘤。10例消化恶性肿瘤术后随访中有3例PET阳性结果与CT/MR相同,4例PET全身显像阴性,另外3例PET显像见其他部位病灶。结论 ~(18)F-FDG PET显像对原发性恶性肿瘤的诊断、良恶性肿块的鉴别诊断具较高的准确性和特异性,对恶性肿瘤治疗后随访确认或排除肿瘤残留和复发以及发现全身部位的转移等具有良好的临床应用价值,其对全身转移病灶的定性和定位诊断优于CT/MR。     

P16在子宫内膜增生过长和子宫内膜癌中的表达和意义

目的　探讨P16蛋白在子宫内膜癌发生和发展中的作用。方法　采用免疫组化法检测P16蛋白在 10例增生期子宫内膜、 10单纯型增生过长、 10例复杂型增生过长、 10例非典型增生过长和 5 0例子宫内膜癌中的表达。结果　在增生期子宫内膜、单纯型增生过长、复杂型增生过长、非典型增生过长和子宫内膜癌中P16的表达依次降低 ,子宫内膜癌中P16的表达与增生期子宫内膜相比 ,差异有显著性 (P <0 .0 5 )。P16在子宫内膜癌中表达在组织学分级G2 G3与G1组 ;有淋巴结转移组与无淋巴结转移组比较 ,差异有显著性 (P <0 . 0 5 )。结论　P16表达与子宫内膜癌的发生发展相关 ,可作为子宫内膜癌的预后指标。     

甲状腺乳头状癌突变等位基因肿瘤异质性的临床及其与预后相关性研究

目的探讨突变等位基因肿瘤异质性(MATH)在甲状腺乳头状癌（PTC）中的临床意义。 方法从癌症基因图谱公共数据集下载并预处理PTC肿瘤测序数据及临床资料数据,分析MATH与PTC临床病理特征的相关性,使用Kaplan-Meier法进行生存分析,验证MATH对PTC患者的预后价值。 结果PTC患者中MATH值为2.57~93.72,平均29.45±16.19;将≥29.45者纳入高MATH组,<29.45者纳入低MATH组。高MATH组与低MATH组的患者年龄、性别、临床分期、BRAF基因型差异无统计学意义（P>0.05）。MATH不是PTC患者总体生存期（OS）的显著预测因素（P=0.4595）;在BRAF突变型PTC患者中,高MATH者的OS低于低MATH者（P=0.0252）,而在BRAF野生型PTC患者中,高MATH者的OS高于低MATH者（P=0.0495）。 结论MATH可在BRAF突变型和野生型亚组中可预测PTC患者的预后及指导临床治疗。     

Macrophages expressing TREM-1 are involved in the progression of HPV16-related oropharyngeal squamous cell carcinoma

IntroductionMany types of research have been performed to improve the diagnosis, therapy, and prognosis of oropharyngeal carcinomas (OP-SCCs). Since they arise in lymphoid-rich areas and intense lymphocytic infiltration has been related to a better prognosis, a TREM-1 putative function in tumour progression and survival has been hypothesized.Materials and methodsTwenty-seven human papillomavirus (HPV) 16⁺ OP-SCC specimens have been analyzed to relate TREM-1 expression with histiocytic and lymphocytic markers, HPV presence and patients’ outcome.ResultsNo differences have been shown between intratumoral and stromal CD4⁺ cells, while intratumoral CD8⁺ lymphocytes are higher with respect to the tumour stroma (p = .0005). CD68⁺ cells are more than CD35⁺ and TREM-1⁺; their presence is related to CD35^± and TREM-1^± histiocytes (p = .005 and .026, respectively). Intratumoral CD4⁺ lymphocytes are higher in p16⁺ cases (11/27) than in p16⁻ (p = .042); moreover, p16 positivity correlates to a better survival (p = .034). CD4⁺, CD8⁺ and CD35⁺ cells have no impact on survival, while CD68 expression heavily influences progression and bad outcome (p = .037). TREM-1 positivity also leads to worst overall survival (p = .001): peritumoral expression and death-cause relationship are always significant, particularly when the cause is OP-SCC (p = .000).ConclusionWhile p16 shows to better stratify HPV16⁺ patients’ outcome, TREM-1⁺ macrophages suggest their key importance in HPV-related OP-SCCs progression.

KEY MESSAGES

• TREM-1 positivity correlates to the worst overall survival of HPV16-positive OPSCCs-affected patients.
• p16-positive HPV16 related OPSCCs patients have a better prognosis with respect to p16-negative ones.

     

The incidence of chromosome 9p21 abnormalities and deletions of tumor suppressor genes p15(INK4b)/p16(INK4a)/p14(ARF) in patients with acute lymphoblastic leukemia

Cytogenetic changes are of pivotal prognostic significance in patients with de novo acute lymphoblastic leukemia (ALL). However, in some cases leukemic blasts can harbor gene lesions on a submicroscopic level without evidence of a corresponding abnormality by conventional cytogenetic studies. This can result in failure to recognize chromosomal abnormalities and inappropriate evaluation with respect to therapy assignments. To study the discrepancy in the detection of deletions of the short arm of chromosome 9 and deletions of tumor suppressor genes p15/p16/p14 on chromosome 9p21, we analyzed bone marrow samples from 92 patients with ALL both by cytogenetic analysis and by Southern blot. In 41 patients (45%), we found deletions of p15/p16/p14, which were homozygous in 27 and hemizygous in 14. Cytogenetic analysis demonstrated abnormalities of the short arm of chromosome 9 in the form of 9p- or del(9p21-22) in only 5 of the 41 patients (12%). Only 2 of 51 patients without gene deletions as detected by Southern blot revealed a 9p- abnormality, which was found only in a subpopulation of the cells. We demonstrate that deletions of the p15/p16/p14 genes on chromosome 9p21 are more frequent than indicated by cytogenetic analysis. Molecular techniques in addition to cytogenetic studies are necessary to detect otherwise-unrecognized genetic lesions of the short arm of chromosome 9.     

Deletion of p16 and p15 genes In schistosomiasis-associated bladder cancer (SABC)

Alterations of p16 and p15 genes have been reported in cancer cell lines and in certain malignant neoplasm. These genes are designated as candidate tumor suppressor genes because they encode proteins that function as negative cell cycle regulators at G₁-S checkpoint. One hundred and sixty eight tumor tissue, 20 schistosomal tissue, and 50 normal tissue samples were examined. The status of p16 and p15 genes in these tissues was determined by the polymerase chain reaction and by sequencing the DNA fragments produced during PCR. In addition, the expression of p16 and p15 proteins was examined by Western blot analysis. p16 and p15 genes were detected in all normal and schistosomal tissues. Deletion of both p16 and p15 genes was observed in 72 and 36 bladder tumors, respectively. Twenty eight of the 72 cases that exhibited p16 deletions also displayed deletions of p15. Only eight cases showed loss of the p15 gene while retaining p16 gene, and p16 deletion with apparently intact p15 gene was identified in 44 cases. The present analysis also reveals that deletion in the two genes are associated with low-stage, low grade bladder cancer, schistosomiasis-associated bladder cancer (SABC) and squamous cell carcinoma type (SCC). No point mutations were identified in either gene. The expression of p16 and p15 proteins was undetectable in 75 and 38 bladder tumors, respectively, by Western blot analysis. Alteration of the p16 and p15 genes appears to be an early event in bladder cancer which occurs more frequently in SABC and SCC, and may play an important role in the development of schistosomal bladder cancer.     

p16和cyclin D_1蛋白在鼻咽癌组织中的表达及其意义

目的　探讨鼻咽癌组织中p16和cyclinD1蛋白的表达及其意义。方法　应用免疫组化S P法检测p16和cyclinD1蛋白在 85例鼻咽癌和 18例鼻咽部炎性黏膜组织中的表达。结果　 85例鼻咽癌中p16的表达率为 41 2 %(35 / 85 ) ;cyclinD1的过表达率为 6 3 5 % (5 4/ 85 )。 18例鼻咽部炎性黏膜中 ,p16的表达率为 10 0 % ;cyclinD1的表达全部为阴性。高分化鳞癌p16的表达率为 75 0 % (6 / 8) ,低分化鳞癌为 38 2 % (2 6 / 6 8) ,两者差异显著 (P <0 0 5 )。有淋巴结转移的p16表达率为 2 8 6 % (14/ 49) ,无淋巴结转移的为 5 8 3% (2 1/ 36 ) ,两者差异非常显著 (P <0 0 1)。 35例p16 ( )的癌组织中有 2 8例cyclinD1呈过表达 ;5 0例p16 (- )的癌组织中有 2 6例cyclinD1呈过表达。结论　p16的缺失表达和cyclinD1的过表达两者可能单独或共同参与了鼻咽癌的发生发展过程。p16的缺失可能还与鼻咽癌细胞的分化、转移有关     

p16在宫颈癌组织中的表达及临床意义

目的 检测p16蛋白在正常宫颈、慢性宫颈炎、CIN和宫颈癌中的表达状况及与临床病理指标的关系,为p16蛋白免疫细胞化学应用于筛查CIN和宫颈癌细胞奠定基础.方法 应用免疫组织化学法检测186例宫颈组织中P16的表达.结果 p16在正常宫颈、慢性宫颈炎、CINⅠ级、CINⅡ-CINⅢ、宫颈癌（鳞癌和腺鳞癌）中的阳性表达率依次增加,其阳性细胞数随病变细胞数增加而增加;p16在上述各组宫颈柱状上皮、间质成纤维细胞、淋巴细胞及相邻的子宫内膜上皮细胞中有一定程度的表达;p16在CINⅡ-CINⅢ级、宫颈癌阳性表达且伴细胞异型性.结论 p16蛋白染色可发现微小宫颈浸润癌;p16蛋白免疫细胞化学结合细胞的异型性可能在液基细胞筛查中有助于诊断来源于鳞状上皮的CIN和宫颈癌（鳞癌和腺鳞癌）细胞.     

抑癌基因P53,nm23,p16独立评价Wilms瘤患儿预后的可能性分析

We studied 22 Wilms'tumors of children immunohistochemically.We've found that the positive rate of p53 in slices was 31.8% (7),of nm23 was 50% (11),and of p16 was 86.4% (19).It suggested that mutation rate of p53 was high in tumors,expression of nm23 in favorite histology(FH)was higher than that in unfavorite histology(UFH) group,and p16 showed very high positive rate in tumors.All of the three showed no relation with sex,age,or pathological type.So each one may be useful in clinic to evaluate pathogenesis and prognosis.     

Expression and significance of p53,nm23 and p16 in Wilms' tumor of children

With the progress in research of cancers,it was found not only oncogene but also supress oncogene was involved in the mutation.p53,p16 and nm23 were three kinds of supress oncogene and contributed to the development of tumors.The mutation,dificency and over expression of aboved genes were common in malignant tumors rather than solid tumors of children.Wu yeming had conducted a lot of studies on embryo bud tumors.The objective of the current study was to furtherly investigate the expression and…     

LAMTOR3 is a prognostic biomarker in kidney renal clear cell carcinoma

ObjectiveThe objective of the study was to investigate the expression of LAMTOR3 in kidney renal clear cell carcinoma (KIRC) and its clinical significance.MethodsThe expression of LAMTOR3 in KIRC and its relationship with clinical features were analyzed using the UALCAN online database. The results were verified using KIRC gene chip data and clinical specimens. The prognosis of KIRC patients was analyzed with the GEPIA2 database. GO, KEGG, and GSEA analyses were conducted to analyze the possible molecular mechanism of LAMTOR3 in KIRC. Immunohistochemical (IHC) and hematoxylin and eosin (H&E) staining were used for histopathological detection.ResultsUALCAN database analysis showed that LAMTOR3 expression in KIRC was significantly lower than in normal kidney tissues and correlated with the clinical stage, pathological grade, and tumor genotype (p < .05). {"type":"entrez-geo","attrs":{"text":"GSE53757","term_id":"53757"}}GSE53757 dataset analysis consistently showed that the expression of LAMTOR3 in KIRC was significantly lower than in normal kidney tissues (p < .01). GEPIA2 database analysis indicated that patients with low LAMTOR3 expression had poor overall and disease‐free survival rates. GSEA analysis suggested that LAMTOR3 positively regulated the citrate cycle and drug metabolism cytochrome P450 and negatively regulated folate biosynthesis and olfactory transduction. The expression of LAMTOR3 in KIRC was also significantly correlated with immune cell infiltration. Finally, IHC showed that LAMTOR3 expression in the KIRC tissues was lower than in the adjacent normal tissues.ConclusionLAMTOR3 expression is significantly lower in KIRC. LAMTOR3 may be a potential marker for KIRC diagnosis and therapy.     

p16基因mRNA及其编码蛋白在人乳腺癌中的表达

目的 探讨人乳腺癌中ｐ１６基因ｍＲＮＡ及其编码蛋白的表达水平与肿瘤发生和预后的相关性。方法 采用免疫组化和原位杂交方法分别对１１例乳腺良性肿瘤和５９例乳腺癌中的ｐ１６基因及其编码蛋白进行检测。结果 ｐ１６基因蛋白表达水平与乳腺肿瘤的良、恶性显著相关（Ｐ〈０．０５）;ｐ１６基因ｍＲＮＡ及其蛋白表达水平与乳腺癌的腋窝淋巴结转移呈显著负相关（Ｐ〈０．０５）;而与乳腺癌的术后生存期呈显著正相关（Ｐ〈０．０     

食管鳞状上皮癌变过程中p16与Fhit的表达及其意义

目的 探讨食管鳞状上皮癌变过程中p16与Fhit蛋白表达变化及其相互关系。方法 采用免疫组化SP法对17例正常食管鳞状上皮、16例轻度不典型增生（Ⅰ级组）、16例中度不典型增生（Ⅱ级组）、17例重度不典型增生（Ⅲ级组）、10例原位癌、18例鳞状细胞癌组织中抑癌基因P16及Fhit的蛋白表达进行检测与分析。结果 ①从食管鳞状上皮→不典型增生→原位癌→鳞状细胞癌，随着食管病变的加重，p16及nlit蛋白表达率呈逐渐降低趋势。②正常组除与不典型增生Ⅰ级组相比p16与F11it蛋白表达差异无显著性（P〉0．05）外，正常组与其余各组相比上述指标差异均有显著性（均为P〈0．05）；鳞状细胞癌组与不典型增生Ⅱ组、Ⅲ组、原位癌组相比p16与Fhit蛋白表达差异无显著性（P〉0．05），鳞状细胞癌组与正常组、不典型增生Ⅰ级组比较上述指标差异均有显著性（P〈0．05）。③p16与Fhit蛋白阳性表达率下降趋势一致。结论 p16与Fhit蛋白表达的缺失在食管癌变过程的早期阶段就已经发生。p16与Fhit蛋白表达呈正相关，可能在食管上皮癌变过程中起到协同作用。     

预后营养指数与靶向治疗中晚期肝癌患者的预后关系

目的:探讨预后营养指数(prognostic nutritional index,PNI)对接受靶向治疗的中晚期肝细胞肝癌(肝癌)患者总体生存期的影响.方法:收集2017年1月至2020年5月复旦大学附属中山医院厦门医院肝肿瘤内科收治的90例接受靶向治疗的肝癌患者的临床资料并随访其生存期,根据血生化结果计算PNI值,分...     

Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma

The receptor for advanced glycation end products (RAGE) is involved in a variety of biological processes, including tumorigenisis. Previous studies have demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule – vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were used to explore the RAGE and VEGFR-2 gene expression levels and the protein of VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi-quantification of endothelial cell marker CD34 combined with caldesmon, which was detected by microvessel density (MVD) technique and immunohistochemistry. Tumors were classified as low or high RAGE-expressing using the median as the cut-off. Immunofluorescence staining for RAGE protein was performed as well. Additionally, the median gene expression levels of VEGFR-2 in the tumors were significantly lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28–0.39) compared to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29–0.61), (P = 0.03). The median MVD was significantly lower in the tumors expressing low levels of RAGE, 6.5 (95% CI, 6.21–7.43), compared to the expressing high levels, 7.9 (95% CI, 6.25–8.93), (P < 0.01). Further, a positive association was certified with VEGFR-2 protein levels, P = 0.07. Besides, RCC with high levels of RAGE expression are associated with high VEGFR-2 mRNA/protein levels and a higher density of microvessels; conversely, Kaplan–Meier survival analysis suggests that a significant correlation of elevated RAGE expression with decreased overall survival and metastasis-free survival. Our results establish that RAGE was identified as a potential prognostic biomarker for disease prognosis of RCC.