Expression of p53 protein in laryngeal squamous cell carcinoma and dysplasia: possible correlation with human papillomavirus infection and clinicopathological findings

In order to evaluate the expression of p53 protein in 28 premalignant and 40 malignant squamous cell proliferations of the larynx and its relationship to tobacco consumption, human papillomavirus infection and differentiation grade of the lesions, p53 expression was examined by means of a microwave post-fixation immunohistochemical method using the PAb 240 and PAb 1801 monoclonal antibodies. HPV infection was assessed by non-isotopic in situ hybridization (NISH) and polymerase chain reaction (PCR). A large proportion of carcinomas (77.5%) and dysplasias (61%) expressed p53. No difference was found between differentiation grades of the lesions regarding p53 detection (P>0.1), but moderate or intense p53 expression was more frequent in the carcinomas (P<0.05). A statistical correlation was found between cigarette consumption and both p53 detection and p53 staining intensity (P<0.05 in each case). HPV study revealed HPV 16 and 18 infection only in carcinomas. The frequency was 28% and the physical state of the virus as demonstrated by NISH was integration into the genome. We observed an inverse relationship between HPV infection and p53 expression (P=0.006). Our findings suggest that p53 overexpression is a common and early event which increases in frequency with progression of laryngeal squamous cell carcinoma. The expression of p53 is influenced by tobacco and high-risk types of HPV.     

The retinoblastoma protein/p16 INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma

Stankiewicz E, Prowse D M, Ktori E, Cuzick J, Ambroisine L, Zhang X, Kudahetti S, Watkin N, Corbishley C & Berney D M
(2011) Histopathology 58 , 433–439
The retinoblastoma protein/p16 ^INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma Aims: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell‐cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell‐cycle proteins: p53, p21, p16^INK4A and retinoblastoma (RB) protein. Methods and results: One hundred and forty‐eight PSCC samples were examined immunohistochemically for RB, p16^INK4A, p53 and p21 protein expression. One hundred and two cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours, with HPV16 present in 81%. Basaloid tumours were related strongly to HPV infection (10 of 13), while verrucous were not (three of 13). Fifty‐nine per cent (38 of 64) of usual type SCCs had HPV infection. RB protein correlated negatively (P < 0.0001) and p16^INK4A (P < 0.0001) and p21 (P = 0.0002) correlated positively with HPV infection. p53 did not correlate with HPV infection. Conclusions: HPV infection is present in more than half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual‐type PSSCs correlate with HPV infection, confirming possible separate aetiologies for those tumours.     

Metachronous squamous cell carcinomas evolving from independent oropharyngeal and pulmonary squamous papillomas: association with human papillomavirus 11 and lack of aberrant p53, Rb, and p16 protein expression

Squamous cell carcinoma evolving from squamous papilloma in both the upper and lower respiratory tract in the same patient is uncommon. The molecular mechanisms underlying the progression have not been well investigated. We herein describe a case of squamous cell carcinoma arising from respiratory papilloma in two independent occasions. The patient initially had oropharyngeal squamous cell carcinoma arising in a squamous papilloma at the age of 25 years. He subsequently developed squamous cell carcinoma in the left lower lobe of the lung, which was also associated with squamous papilloma, 8 years after the complete excision of the oropharyngeal lesion. Polymerase chain reaction-based broad-spectrum human papillomavirus DNA amplification and typing showed the presence of human papillomavirus type 11 DNA in both oropharyngeal and pulmonary tumors. Immunohistochemical studies showed that the expression status of p53, Rb, and p16 proteins was unaltered during tumor progression. These observations indicate that human papillomavirus 11-associated neoplastic transformation and tumor progression in the respiratory tract may not involve aberrant regulation of the p53 and Rb signaling pathways.     

Prevalence of high-risk human papillomavirus in primary squamous cell carcinoma of urinary bladder

Studies have demonstrated an etiologic role of high-risk human papillomavirus (HR-HPV) infection for epithelial malignancies, including most cervical carcinomas, anogenital cancers, and carcinomas of the head and neck; however, a causative role of HPV infection for bladder cancer is controversial. The purpose of this study was to investigate the prevalence of HR-HPV in primary bladder carcinoma to determine the association between HPV infection and the squamous cell component of urothelial carcinoma of the bladder. Furthermore, we evaluated the utility of p16 overexpression as a surrogate marker for HPV infection in these cancers and the correlation of this with tumor stage. Our study included 33 cases of squamous cell carcinoma (SCC) of the urinary bladder. Tumors deemed primary from the bladder were selected and either showed predominant (>50 %) or pure squamous differentiation. Immunohistochemical study for p16 and HR-HPV by RNA in situ hybridization (ISH) was performed in all cases. p16 expression was detected in 7 cases (28 %, 7/25) of urothelial carcinoma with squamous differentiation and not detected in any of the 8 cases (0%, 0/8) of pure SCC. Detection of HR-HPV by ISH was negative in all 33 cases (0%, 0/33). There was no association between p16 overexpression and the presence of HPV infection in squamous cell carcinomas of the bladder. p16 should not be used as a surrogate marker for evidence of HPV infection. Our study suggests that HPV infection does not play an etiologic role in the development of bladder cancer and should not be used as a diagnostic adjunct for these cases.     

Prognostic significance of p53 and p63 immunolocalisation in primary and matched lymph node metastasis in oral squamous cell carcinoma

This study evaluates the prognostic significance of p53 and p63 immunolocalisation in oral squamous cell carcinoma samples from 45 matched primary tumors (PT) and lymph node metastases (LNM). Data regarding patient age, gender, primary site, histological differentiation, metastasis, disease-free survival (DFS) and overall survival (OS) were available. p53 and p63 immunolabeling was detected in 17 (37.8%) and 23 (51.1%) of the PT, respectively. For LNM, there was p53 and p63 labeling in 23 (51.1%) and 26 (57.8%) cases, respectively. Most cases showed similar labeling in PT and the corresponding LNM (73.3% for p53 and 53.3% for p63, respectively). No statistically significant associations were found between p53 and p63 immunolabeling and histological differentiation; p63 positive tumors showed higher DFS (p=0.006) and OS (p=0.049); and p53-negative tumors had a higher DFS interval (p=0.009). Our findings suggest that initially p53-negative tumors and initially p63-positive tumors that retain this labeling pattern may follow less aggressive biological courses and present better prognoses.     

Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16(INK4A) overexpression and clinicopathological correlations

Fuste V, del Pino M, Perez A, Garcia A, Torne A, Pahisa J & Ordi J
(2010) Histopathology 57, 907–916 Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16 ^INK4A overexpression and clinicopathological correlations Aim: To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance. Methods and results: All cases of SCCVa diagnosed over a 15‐year period from two hospitals in Barcelona, Spain (n = 32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed <5 years before were excluded. HPV was detected and typed by polymerase chain reaction (PCR) using SPF10 primers. Immunohistochemistry was performed for p16 and p53. HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV‐positive tumours were associated frequently with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% versus 0%; P = 0.01). HPV‐positive tumours were more frequently of non‐keratinizing, basaloid or warty type than HPV‐negative neoplasms (84% versus 14.3%; P < 0.001), and showed diffuse positive immunoreactivity for p16^INK4a (96%, versus 14.3%; P < 0.001). The sensitivity and specificity of p16 to identify HPV‐positive tumours were 96% and 85.7%, respectively. Conclusions: A high number of SCCVs are related to HPV infection and may be identified by immunohistochemistry for p16. HPV‐positive tumours tend to affect women with history of cervical neoplasia.     

High frequency of coexpression of maspin with p63 and p53 in squamous cell carcinoma but not in adenocarcinoma of the lung

Maspin, a member of the serpin family of protease inhibitors, has been shown to inhibit tumor growth and suppress metastasis in several malignancies, including lung cancer. Previous studies have reported that p63 and p53 control maspin expression by transactivating the promoter. The present study analyzed immunohistochemical studies to determine the expression and coexpression patterns of maspin, p63 and p53 in non-small cell lung carcinoma, specifically squamous cell carcinoma and adenocarcinoma. The results showed that 83/86 cases (96.5%) of squamous cell carcinoma and 82/161 cases (50.9%) of adenocarcinoma included in this study were positive for maspin. There were 79/86 cases (91.9%) of squamous cell carcinoma and 16/161 cases (9.9%) of adenocarcinoma with positive expression for p63. In addition, 77/86 cases (89.5%) of squamous cell carcinoma and 99/161 cases (61.5%) of adenocarcinoma were positive for p53. Maspin, p63 and p53 expression were each significantly higher in squamous cell carcinoma than adenocarcinoma. Squamous cell carcinomas more highly coexpress maspin and p63, as well as maspin and p53, when compared with adenocarcinomas. The high frequency of coexpression of maspin and p63, as well as maspin and p53, in squamous cell carcinoma, suggests that p63 and p53 may be involved in the pathway to control maspin expression. Therapeutic targeting on maspin, p63 and p53 molecules might be beneficial in the management of patients with squamous cell carcinomas of the lung in the future.     

Overexpression of p16 and p14ARF is associated with human papillomavirus infection in cervical squamous cell carcinoma and dysplasia

The CDKN2 gene encodes two structurally different proteins: a cyclin-dependent kinase inhibitor, p16, which regulates retinoblastoma protein (pRb)-dependent G1 arrest, and a cell cycle inhibitor, p14ARF, which blocks MDM2-induced p53 degradation resulting in an increase in p53 levels that leads to cell cycle arrest. Recent studies have revealed that expression of p16 and p14ARF is influenced markedly by the status of pRb and p53, and p16 overexpression has been demonstrated in cervical neoplasia because of functional inactivation of pRb by the human papillomavirus (HPV) E7 protein. To clarify the p14ARF status and the relationship between p16/p14ARF and other cell cycle molecules in cervical carcinogenesis, immunohistochemical analysis of p16, p14ARF, p53 and MDM2 was performed on 65 samples of cervical and genital condylomatous and neoplastic lesions, including nine HPV-negative tumors. In most cervical cancers and preneoplastic lesions with HPV infection of high and intermediate risk, a marked overexpression of p14ARF as well as the p16 protein (i.e. dotted nuclear immunostaining) was observed. All condyloma acuminata except one and low-grade dysplasia with HPV infection of low risk, such as HPV 6, immunohistochemically showed completely negative staining for p14ARF, also seen in non-neoplastic and mesenchymal cells. Our results clearly show that the mode of p14ARF overexpression in cervical neoplastic cells with HPV association differs from that in cancers of other organs without HPV association, and the p14ARF overexpression may be attributable to a negative feedback result in the functional inactivation of the pRb and p53 proteins by HPV oncoproteins.     

Expression of p21/WAF-1, status of apoptosis and p53 mutation in esophageal squamous cell carcinoma with HPV infection

Human papilloma virus (HPV) is regarded as a causative carcinogenic agent in anogenital squamous cell carcinoma (SCC), but there is controversy about its etiologic role in esophageal SCC (ESCC). In this study, we attempted to clarify whether HPV infection plays a crucial role in the development of ESCC by analysis of multiple factors. These included: detection of HPV DNA; evaluation of immunohistochemical assays for HPV-related cell cycle regulators and apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method; and genetic analysis of the p53 gene. Twenty of the 48 ESCC examined (42%) were found to be positive for the HPV genome by polymerase chain reaction. They comprised 16 cases with the HPV16 subtype, three with the HPV18 subtype, and one with both HPV16 and 18. Immunohistochemical analysis revealed that the expression of p21/WAF-1 was significantly decreased in HPV-positive cases (chi2 = 9.2614; P = 0.0023). Furthermore, the 10 apoptosis-negative (< or =10%) cases of HPV-positive SCC were almost exclusively p21/WAF-1-negative (chi2 = 12.1406; P = 0.0005), indicating the significance of the relationship between HPV infection and the phenotype that is expected from HPV-induced inhibition of p53. Although 14 cases possessed missense and deletion mutations of the p53 gene (of which four mutations were found in HPV-positive ESCC), no accumulation of the mutation was defined in the phenotype, suggesting that distinct mutation processes might be involved in HPV-negative and -positive ESCC. The data provide significant support for the hypothesis that HPV infection may play a crucial role in the oncogenesis of some ESCC.     

The relationship between p16 expression and high-risk human papillomavirus infection in squamous cell carcinomas from sites other than uterine cervix: a study of 137 cases

p16 is known to be an excellent surrogate marker of human papillomavirus infection in squamous cell carcinoma of the cervix. Recent studies have demonstrated a link between human papillomavirus infection and a subset of head and neck squamous cell carcinomas, especially from the oropharynx. The aims of this study were to determine the incidence of p16 expression in squamous cell carcinomas of noncervical origin and to assess its utility as a surrogate marker of human papillomavirus infection in various noncervical primary sites. One hundred thirty-seven squamous cell carcinomas from 5 primary sites, including 34 from the oropharynx (tonsil and base of tongue), 43 cases from nonoropharyngeal head and neck sites, and 20 cases each from the lung, esophagus, and skin, were retrieved from our surgical pathology archives. Immunohistochemistry for p16 was performed on each case. All p16-positive cases and 21 p16-negative cases were further tested for both high-risk and low-risk human papillomavirus by in situ hybridization. p16 expression was detected in 54 cases overall, including 25 (74%) of 34 oropharyngeal squamous cell carcinomas, 8 (19%) of 43 nonoropharyngeal head and neck squamous cell carcinomas including 3 of 4 from the sinonasal cavity, 6 (30%) of 20 esophageal squamous cell carcinomas, 7 (35%) of 20 lung squamous cell carcinomas, and 8 (40%) of 20 skin squamous cell carcinomas. Of the 54 p16-positive cases, 30 were positive for high-risk human papillomavirus, including 24 (96%) of 25 from the oropharynx, 5 (63%) of 8 from nonoropharyngeal head and neck sites, and 1 (17%) of 6 from the esophagus. All 7 lung and 8 skin cases tested were negative. All p16-positive cases were negative for low-risk human papillomavirus. In selected head and neck squamous cell carcinomas, mainly from the oropharynx and sinonasal cavity, p16 positivity correlates well with high-risk human papillomavirus infection. p16 is not a reliable indicator of high-risk human papillomavirus infection in squamous cell carcinomas of the lung, skin, and esophagus.     

Expression of the GLUT1 glucose transporter, p63 and p53 in thyroid carcinomas

Only few studies have evaluated the usefulness of the GLUT1 and p63 status of thyroid carcinomas in revealing tumorigenesis. We studied GLUT1, p53, and p63 immunoexpression in a total of 86 cases of various thyroid carcinoma types to determine the biological significance of GLUT1 and p63 expression in thyroid carcinomas. GLUT1 was detected in six cases of anaplastic carcinoma and in one case of poorly differentiated carcinoma with membranous staining. p63 was detected in five cases of anaplastic carcinoma, in one case of poorly differentiated carcinoma, and in five cases of papillary carcinoma with nuclear positivity. p53 was detected in six cases of anaplastic carcinoma, in one case of poorly differentiated carcinoma, and in one case of follicular carcinoma with nuclear positivity. Five of seven cases of anaplastic carcinoma expressed all three of these markers. The results suggest that GLUT1, p63, and p53 are not expressed in well-differentiated thyroid carcinomas, and that they are usually expressed late in the course of thyroid tumor progression. These data strongly suggest that in anaplastic carcinomas, impairment of p53-mediated repression results in increased GLUT1 and p63 expression, and that this probably reflects the differential regulation of hypoxia-responsive pathways and basal/stem cell regulatory pathways.     

Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53 . We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion ( P = 0.032) or metastatic disease ( P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells ( P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells ( P = 0.05).
Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.     

宫颈鳞癌中p16、p21WAF1、Rb、cyclinE蛋白的表达

目的通过观察p16、p21WAF1、Rb、cyclinE 4种细胞周期相关蛋白在宫颈鳞状细胞癌中的表达,探讨它们在宫颈癌的细胞周期调控中的作用.方法采用免疫组化Eli Vision二步法对88例宫颈鳞癌组织,16例宫颈上皮内病变(CIN)组织,15例宫颈炎组织进行p16、p21WAF1、Rb、cyclinE 4种蛋白表达的检测.结果p16、p21WAA1、cyclinE在宫颈癌中的表达高于宫颈炎(P＜0.05);Rb在宫颈癌的表达少于宫颈炎(P＜0.05);Rb与p16在宫颈癌中的表达呈负相关(r=-0.675,P＜0.05).结论宫颈癌细胞周期G1期中,由于Rb蛋白的缺失,使cyclinE表达升高,致使癌细胞增生;同时,p16、p21WAF1蛋白在宫颈癌中的表达增高,并失去抑制作用.     

Human papillomavirus infection is not associated with laryngeal squamous cell carcinoma in Taiwan

Background/PurposeTo examine whether the prevalence rate of human papillomavirus (HPV) infection in Taiwanese patients with primary laryngeal squamous cell carcinoma (LSCC) is different from that in those with a vocal polyp (VP) or vocal fold leukoplakia (VFL).MethodsThis prospective cohort study recruited 41 consecutive patients with primary LSCC and 27 and 20 patients with VP and VFL, respectively. The HPV L1 gene in surgical specimens was detected using polymerase chain reaction. High-risk HPV DNA in tissue microarray specimens was detected using in situ hybridization. Expression of p16^INK4a in tissue microarray specimens was determined through immunohistochemistry.ResultsThe prevalence of HPV L1 DNA in the LSCC group was equivalent to that in the VP and VFL groups (7.3% vs. 7.4% vs. 10.0%; P = 0.929; effect size = 0.20). High-risk HPV DNA detected using in situ hybridization was relatively rare in all groups (2.6% vs. 5.3% vs. 0.0%; P = 0.636; effect size = 0.81). The prevalence of p16^INK4a positivity was significantly lower in the LSCC group than in the VP and VFL groups (5.1% vs. 58.8% vs. 14.3%; P < 0.001). Multivariate analysis results revealed that age ≥65 years (adjusted odds ratio, 4.09; 95% confidence interval, 1.21–13.91; P = 0.024) and p16^INK4a positivity (adjusted odds ratio, 0.10; 95% confidence interval, 0.02–0.53; P = 0.006) were LSCC risk factors.ConclusionHPV infection is uncommon in Taiwanese patients with LSCC and seems not to be associated with an increased LSCC risk. Larger sample size is warranted for further study.     

Immunohistochemical detection of p53 in cervical epithelial lesions with or without infection of human papillomavirus types 16 and 18

Using formalin-fixed and paraffin-embedded cervical tissues, we examined infection with human papillomavirus (HPV) types 16 and 18 by Southern blot analysis following polymerase chain reaction (PCR), and the accumulation of p53 protein by immunohistochemistry in 30 cases of normal or metaplastic cervix, 17 cases of cervical intraepithelial neoplasia grade I (CIN I), 20 cases of CIN II, 37 cases of CIN III and 23 cases of invasive squamous cell carcinoma (ISCC). In addition, we examined the ratio of HPV-infected cells by in situ hybridization (ISH) and the alteration of p53 gene using PCR followed by single-strand conformation polymorphism (PCR-SSCP) in 2 cases of CIN III and 12 cases of ISCC, in which overexpression of p53 was immunohistochemically detected. HPV DNA was detected in 5 cases (16.7%) of normal or metaplastic cervix, 5 cases (29.4%) of CIN I, 9 cases (45.0%) of CIN II, 26 cases (70.3%) of CIN III and 15 cases (65.2%) of ISCC. Positivity for HPV in the groups of CIN III and ISCC was significantly higher than in the normal or metaplastic cervix (P<0.05). The accumulation of p53 was not detected in the normal or metaplastic cervix, CIN I and CIN II. High-level p53 accumulation was identified in basal and suprabasal atypical cells in 27.0% (10/37) of CIN III and in carcinoma cells in 43.5% (10/23) of ISCC cases, and low-level accumulation was identified in atypical cells of 35.1% (13/37) of CIN III and in carcinoma cells in 30.4% (7/23) of ISCC cases. The accumulation of p53 was found to coexist with infection by HPV in 17 (46.0%) of 37 CIN III cases and 12 (52.2%) of 23 ISCC cases, and high-level p53 accumulation was more frequently detected in HPV-positive ISCC cases. Either HPV infection or accumulation of p53 was found in 16.7% (5/30) of the cases of normal or metaplastic cervix, 29.4% (5/17) of CIN I, 45.0% (9/20) of CIN II, 86.5% (32/37) of CIN III and 87.0% (20/23) of ISCC cases. These results suggest that the inactivation of p53 function by HPV infection or alteration of p53 protein itself precedes the development of tumours with a fully malignant and invasive phenotype and plays an important role in tumorigenesis in the uterine cervix. ISH study provided no correlation between the degree of immunohistochemical positivity for p53 and the ratio of HPV-positive cells in the same lesions. PCR-SSCP detected the alteration of p53 gene in at least 4 cases of ISCC, 2 of which were accompanied by HPV infection.     

p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma

p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors (P < .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration (P < .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression (P < .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.     

Search for accumulation of p53 protein and detection of human papillomavirus genomes in sebaceous gland carcinoma of the eyelid

Twenty-one Japanese patients with sebaceous carcinoma of the eyelid were investigated for tumour incorporation of human papillomavirus (HPV) types-6, 11, 16, 18, 31, and/or 33 DNA by in situ hybridization with fluorescein isothiocyanate-labelled DNA probes, and for p53 protein accumulation by immunohistochemical analysis with an antibody to p53 protein. Thirteen tumours (61.9%), including 9 cases of multiple infections, were positive for HPV DNA. Positive signal in the nucleus was observed not only in the cancer cells, but also in the cells of surrounding normal sebaceous glands and epidermis. Positive nuclear staining of cancer cells with the antibody to p53 protein was detected in 12 cases (57.1%). p53 protein accumulation was more frequently observed in the clinically advanced cases, occasionally in association with recurrence and/or metastasis. Among the 12 p53-positive cases, 7 were also positive for the presence of HPV DNA. HPV infections exist in a high percentage of sebaceous carcinomas of the eyelid in Japan; the overexpression of p53 protein may be important in both carcinogenesis and progression.     

宫颈鳞状细胞癌HPV16/18、p53、p21表达及意义

目的　探讨人乳头状瘤病毒 (HPV) 16型、18型及 p5 3、p2 1基因蛋白的表达情况以及与宫颈癌的关系。 方法　应用免疫组化二步法检测 5 0例宫颈鳞癌、4 0例正常宫颈黏膜中HPV16、HPV18、p5 3、p2 1的表达。肿瘤组分 <6 0岁和≥ 6 0岁 2个年龄组 ,观察HPV感染情况。结果　宫颈鳞癌中HPV16、HPV18、p5 3、p2 1表达分别为 4 8%、2 0 %、5 4 %和 5 0 % ,而正常宫颈黏膜中的表达分别为 10 %、0、0、10 % ,两者经统计学比较差异有显著性 (P <0 0 1) ;<6 0岁组和≥ 6 0岁组HPV16阳性率分别为 84 2 %和 2 5 8% ,年青组明显高于年老组 ,经统计学比较差异有显著性 (P <0 0 1)。结论　 (1)宫颈鳞癌的发生与HPV16、HPV18感染有密切关系 ,提示检测宫颈HPV16、HPV18感染情况对于宫颈鳞癌的随访和早期诊断有着重要的参考价值。 (2 )提示宫颈黏膜在HPV感染后 ,可能在p5 3、p2 1多种癌基因的共同作用导致宫颈鳞癌的发生发展。