Differentiation-related p53 protein expression in nondysplastic sinonasal inverted papillomas.

To clarify p53 protein expression in nondysplastic sinonasal inverted papillomas, archived surgical specimens from 19 patients were studied using immunohistochemistry. Staining results were compared between inverted papillomas and adjacent, nonpapillomatous nasal mucosa. Further, immunoreactivity was compared between columnar (respiratory), transitional (cuboidal), and squamous epithelium in inverted papillomas. Positive staining was found in 17 of 19 inverted papillomas (89%). Immunoreactivity involved predominantly basal and parabasal cells and was either comparable or higher in inverted papillomas compared with adjacent mucosa. In 65% of immunoreactive inverted papillomas comparable staining results were seen between columnar (respiratory), transitional (cuboidal), and squamous epithelium. In 35% of p53 protein-positive inverted papillomas, enhanced immunoreactivity was observed in transitional (cuboidal) and squamous epithelium compared with columnar (respiratory) epithelium. Within these cases, immunoreactivity was either comparable or higher in squamous compared with transitional (cuboidal) epithelium. Conclusively, the expression of p53 protein is present in 89% of nondysplastic sinonasal inverted papillomas and also involves the adjacent, nonpapillomatous nasal mucosa. A tendency toward increasing p53 protein expression from nonpapillomatous nasal mucosa to inverted papilloma as well as along the metaplastic process from columnar (respiratory) to transitional (cuboidal) and finally squamous epithelium within inverted papillomas can be postulated.     

Schneiderian papillomas and carcinomas: a retrospective study with special reference to p53 and p16 tumor suppressor gene expression and association with HPV

Schneiderian papillomas are uncommon benign tumors of the sinonasal area. They are prone to local aggressiveness and recurrence, and some undergo malignant progression. We analyzed specimens obtained from 67 Chinese patients who had presented to the ENT department of a regional hospital with biopsy-proven schneiderian papilloma. Seven of these patients had either synchronous or metachronous carcinoma, 1 of whom had pure carcinoma in situ. For each case, we documented the morphology, immunohistochemical expression of tumor suppressor genes p53 and p16, and any association with human papillomavirus (HPV) infection as detected by either polymerase chain reaction or in situ hybridization techniques. We found that severe dysplasia and p53 positivity were strongly associated with malignant progression. Association with HPV was demonstrated in 22 of the 67 patients (33%); the association was strongest among patients with exophytic papillomas and carcinomas. The effect of HPV in papilloma oncogenesis probably begins during the early phase, while other factors are responsible for progression to carcinoma. We conclude that p53-positive, dysplastic schneiderian papillomas warrant aggressive surgical treatment.     

Temporal bone and sinonasal inverted papilloma: the same pathological entity?

BACKGROUND: Inverted papilloma involving the temporal bone is an extremely rare occurrence. Reports in the literature suggest a higher recurrence rate and association with squamous cell carcinoma in Schneiderian-type papillomas of the middle ear than in sinonasal Schneiderian-type papillomas. OBJECTIVES: To investigate the expression of apoptosis-related proteins, markers of cell proliferation activity, and sex hormone receptors in temporal bone inverted papillomas and to compare this entity with sinonasal papillomas.Design and Subjects We investigated 2 rare cases of inverted papilloma of the temporal bone and a control group of 6 cases of sinonasal inverted papilloma. The expression of p53, Mib-1, p27, and progesterone and estrogen receptors was determined. RESULTS: In the 2 cases of temporal bone inverted papilloma, p53 expression was 43.75% and 4.92%; p27 expression was higher in temporal bone inverted papilloma (82.45% and 70.53%) than in the sinonasal inverted papilloma group. One of our 2 cases of temporal bone Schneiderian-type papilloma was positive for progesterone receptor. CONCLUSIONS: The expression of progesterone receptor in 1 of our 2 cases and in the only other case reported in the literature may imply some degree of hormonal dependence of temporal bone inverted papilloma. Our analysis of the expression of apoptosis-related proteins, markers of cell proliferation activity, and sex hormone receptors does not allow us to demonstrate that temporal bone and sinonasal inverted papilloma are different pathological entities.     

Sinonasal Papillomas: Clinicopathologic Review of 40 Patients With Inverted and Oncocytic Schneiderian Papillomas

Objective To evaluate the pathological features and variations of sinonasal inverted and oncocytic papillomas and correlate the microscopic findings with the clinical behavior. Study Design A retrospective review and pathological assessment. Methods A retrospective review and pathological assessment were performed on 40 patients with a diagnosis of inverted papilloma treated by the senior author (w.l.) between 1994 and 2001. Results Forty cases were identified and reviewed. Seven patients developed recurrences (18%), and four underwent malignant transformations (10%). Pathological assessment revealed 34 (85%) inverted papillomas and 6 (15%) oncocytic schneiderian papillomas. Dysplasia was present in 26 cases (65%), including 9 cases (22%) of high‐grade dysplasia (moderate to severe). Metaplasia of the sinonasal mucosa adjacent to inverted papillomas and oncocytic schneiderian papillomas was seen in 18 (45%) cases. Recurrence developed in two patients with oncocytic schneiderian papillomas (33%) and five patients with inverted papillomas (15%). Four cases (10%) of carcinoma ex papilloma were seen; one arose from oncocytic schneiderian papilloma (17%), and three arose from inverted papilloma (9%). Oncocytic schneiderian papilloma was more often mixed with typical inverted papilloma, rather than presenting in its pure form. Conclusions Although oncocytic schneiderian papilloma is uncommon relative to inverted papilloma, the results suggest that they have higher rates of both recurrence and malignant transformation. The common admixture of oncocytic schneiderian papilloma with inverted papilloma speaks for a common etiological factor of these two lesions. A larger number of cases for analysis would be necessary to confirm the trend noted in our data. Nonetheless, pathological findings consistent with oncocytic schneiderian papilloma should be explicit in any classification system and justify aggressive treatment and careful postoperative surveillance.     

Schneiderian carcinoma developing in an inverted papilloma of the palatine tonsil: an unusual case

Schneiderian papillomas are among the most common benign tumors of the nose and paranasal sinuses. These lesions frequently originate in the lateral nasal wall, and they have a tendency toward recurrence and malignant transformation. Carcinomas arise in association with schneiderian papillomas in approximately 10% of cases. Outside the sinonasal tract, the ectopic occurrence of a schneiderian papilloma is extremely rare. We describe the case of a 52-year-old man with an invasive schneiderian carcinoma that arose within an inverted papilloma in the palatine tonsil. To the best of our knowledge, no such case has been previously reported in the English-language literature.     

鼻内翻性乳头状瘤及其癌变与p53蛋白异常表达

目的：探讨鼻内翻性乳头状瘤及其癌变与ｐ５３基因的关系。方法：采用免疫组化方法（ＡＢＣ法）对３６例鼻内翻性乳头状瘤（ＩＰ）组织和１６例鼻内翻性乳头状瘤癌变（ＩＰ＋ＳＣＣ）组织进行了ｐ５３蛋白检测。结果：３６例ＩＰ均为ｐ５３蛋白阴性，而在１６例ＩＰ＋ＳＣＣ组织中有５例为ｐ５３蛋白阳性，阳性率为３１．３％（５／１６），经统计学处理，二者差异显著（Ｐ〈０．００１）。结论：ｐ５３蛋白异常表达可能与ＩＰ的发生     

Minimally invasive treatment of the nasal inverted papilloma

BACKGROUND: The purpose of this work is to evaluate our results in the treatment of the nasal inverted papillomas with an endoscopic approach using a retrospective case series. METHODS: Between 1993 and 2000 we treated 27 patients with nasal inverted papillomas. All patients underwent endoscopic nasal surgery under general anesthesia. None of the inverted papillomas extended outside of the paranasal sinuses. All tissue samples underwent polymerase chain reaction and hybridization in situ to detect genetic sequences of the human papilloma virus and Epstein Barr virus. RESULTS: The study population consisted of 16 men and 11 women with a median age of 52 years (range, 22-77 years). Ten patients (37%) had undergone a previous nasal surgery. The median follow-up was 5 years (range, 2-8 years). None of the patients presented with bilateral nasal involvement or a synchronous carcinoma. Seven patients underwent an additional surgical approach (two endoscopic approaches via a Caldwel-Luc approach, four sublabial approaches via a Caldwel-Luc approach, and one external ethmoidectomy). There were no surgical complications. Two patients (7%) had recurrent papilloma 4 and 6 years after surgery and again underwent endoscopic resection. The amplification both by polymerase chain reaction and hybridization in situ for human papilloma virus and Epstein Barr virus were negative in the specimens from all patients. CONCLUSIONS: According to the literature and our own experience, we believe that the initial surgical management of primary and recurrent inverted papillomas limited to the nasal cavity and paranasal sinuses should be endoscopic sinus surgery.     

Expression patterns of p27Kip1 and Ki-67 in cholesteatoma epithelium

OBJECTIVES: The cell cycle must be involved in cell proliferation of the epithelium of middle ear cholesteatoma Cyclins and cyclin-dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression. Cyclin-CDK complexes are in turn regulated by the cyclin-dependent kinase inhibitors (CDKIs), which generally inhibit cell cycle progression. One of the important CDKI members is p27(Kip1). The goal of this study is to evaluate the expression of p27(Kip1) and Ki-67, a proliferation marker, in cholesteatoma and in the skin of the external ear canal. METHODS: The expressions of p27(Kip1) and Ki-67 in cholesteatoma epithelium (n = 20) and ear canal epithelium (n = 7) were investigated by an immunohistochemical technique. RESULTS: In cholesteatoma epithelium specimens, the expression of p27(Kip1) was observed from the parabasal layer to the granular layer, but not in the basal layer. Ki-67 was expressed dominantly in the basal and parabasal cell layers. Their expressions tend to be increased compared with their expressions in the normal ear canal skin. The expression pattern of the proliferation marker Ki-67 in the epithelial layers of two groups was inversely related to the expression of p27(Kip1). CONCLUSIONS: In cholesteatoma, the expressions of CDKI and Ki-67 were both increased in this study. The ability to inhibit proliferative activity was also increased in the cholesteatoma epithelium. The expression pattern of the proliferation marker Ki-67 in the epithelial layers was inversely related to the expression of p27(Kip1). Not only is the proliferation activity increased, but also the ability to inhibit hyperproliferation is increased in the cholesteatoma epidermis. Despite increased proliferative activity in the cholesteatoma epidermis, epithelial cells still retain the capability to prevent cell cycle arrest by means of p27(Kip1).     

Expression of the the cyclin-kinase inhibitors p21(WAF1) and p27(Kip1) and the p53 tumor suppressor genes in adult-onset laryngeal papillomas

Different types of human papilloma virus are known to be closely associated with laryngeal papillomas. On the other hand, the proliferation of epithelial cells is associated with various abnormalities in the mechanisms of cellular regulation. In this study, we detected the expressions of p53, p21 and p27 proteins in adult-onset laryngeal papillomas by immunohistochemical techniques. The objective of this study is to evaluate the expression of these factors in adult-onset laryngeal papillomas and to determine whether such expression is correlated with the existence of dysplastic epithelium covering the papillomas. Eighteen patients with adult-onset papillomas who were surgically treated at the Department of Otolaryngology at the University of Istanbul between January 1994 and December 1999 were included in this study. Anti-p21, -p27 and -p53 antibodies were used to perform immunostaining. Positive nuclear staining for p21 was detected in 14 of the 18 (78%) cases, especially in the parabasal layer. Also, in 78% of the cases, weak to strong immunoreactivity was observed for p27. In all cases, negative immunoreactivity was observed for p53 throughout the epithelium except for the basal and parabasal cells. A negative correlation was observed between the existence of dysplastic epithelium and p21 expression (P=0.02). In conclusion, variable p21 and p27 expression was detected by immunohistochemistry in our series of 18 cases of adult-onset laryngeal papillomatosis, and a statistically significant inverse correlation was detected between p21 expression and the existence of dysplastic epithelium covering the papillomas. Further prospective studies are warranted to determine the prognostic values of these variables and to evaluate their role in the pathogenesis of adult-onset laryngeal papillomas.     

Evaluation of p53, p63, p21, p27, ki-67 in paranasal sinus squamous cell carcinoma and inverted papilloma

Using a molecular genetic approach, we try to confirm the molecular alterations of inverted papilloma and clarify its status as a putative precursor lesion of sinonasal squamous cell carcinoma. To better understand its genetics, we investigated the immunohistochemical protein expression patterns of cell-cycle-regulators p53, p63, p21, p27 and proliferation marker Ki-67 in 22 inverted papilloma and 9 squamous cell carcinoma of the sinonasal tract. Significantly elevated levels of p53 and p63 in squamous cell carcinoma of sinonasal tract compared with inverted papilloma were revealed. Ki-67-stained neoplastic cell nuclei were found in a significantly higher percentage of squamous cell carcinoma of sinonasal tract than in inverted papilloma, whereas no variation of p21 and p27 expression was identified. This work first examined the immunohistochemical overexpression of p63 in sinonasal inverted papilloma and squamous cell carcinoma. In conclusion, this is a first study shedding light on the expression of p63 in tumors of paranasal sinuses.     

Inverted schneiderian papilloma of the supraglottis: Case report

Inverted schneiderian papillomas are rare benign tumors, most often arising from the sinonasal mucosa. We describe a case of a 59‐year‐old female with an inverted papilloma of the supraglottis. This is the first reported case of a supraglottic‐presenting inverted papilloma. Although rare, this case demonstrates that these tumors should be considered during workup of supraglottic laryngeal masses. Laryngoscope, 127:2830–2832, 2017     

Inverted papilloma of the nose and paranasal sinuses: a study of 67 patients

Retrospectively, 67 patients with inverted nasal papillomas were studied. In 12, the lesions were localized exclusively on the nasal septum. In 55, the lesion involved the lateral wall and/or the paranasal sinuses. There was a male predominance of 3:1. After histological revision the most dominating epithelial type was found to be transitional. Inverted papilloma was in one patient associated with squamous cell carcinoma. Ten per cent suffered recurrences from 6 to 37 months after the primary surgical procedure. We found that limited septal lesions could be managed by an intranasal procedure but lateral rhinotomy is recommended as the procedure of choice in the treatment of inverted papilloma of the lateral wall.     

增殖细胞核抗原和p27在鼻内翻性乳头状瘤中的表达

目的 检测鼻内翻性乳头状瘤(nasal inverted papilloma,NIP)组织中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和p27蛋白表达,从细胞增殖状况和细胞周期调控方面探讨NIP发生、生长机制.方法 应用免疫组织化学LSAB法检测47例NIP、49例鼻息肉、43例鼻鳞状细胞癌、11例正常鼻黏膜组织中PCNA和p27蛋白的表达.结果 NIP组PCNA标记指数(labelling index,LI)高于鼻息肉组及正常鼻黏膜组(P＜0.001),与鼻鳞状细胞癌组差异无统计学意义(P＞0.05),NIP中初发组与复发组之间差异无统计学意义(P＞0.05);p27蛋白在各实验组中均有部分表达,各组间差异无统计学意义(P＞0.05).结论 PCNA指数可以反映NIP的增殖状况,但其与NIP的复发无明显关系;而p27在NlP发展过程中的作用尚需进一步探讨.     

Schneiderian papillomas of the pharynx

Sixteen cases of schneiderian-type mucosal papillomas arising in the nasopharynx and oropharynx are reported. The patients include 11 men and 5 women ranging in age from 45 to 79 years (median 62 years). In 12 patients, the papilloma was discovered as an incidental finding, and 2 patients complained of nasal airway obstruction. In the remaining 2 cases, information regarding the cause that led to discovery was unavailable. None of the patients had a prior or concurrent history of sinonasal (schneiderian) papillomas. Histologically, all of the tumors were identical to sinonasal inverted papillomas. Transnasal or transoral surgical excision was the treatment of choice. In 4 of the patients, recurrent tumor occurred within 6 months of initial resection, necessitating additional surgery. Extended follow-up information was available in 9 cases. Eight of the 9 patients are alive and have been free of disease over periods ranging from 15 to 201 months (median 114 months) from diagnosis. One patient was found to have a separate nasopharyngeal squamous cell carcinoma 14 months after the diagnosis of the schneiderian-type papilloma. This patient died secondary to the squamous cell carcinoma 30 months after his initial evaluation.     

Expression of cell cycle regulatory proteins and analysis of apoptosis in normal nasal mucosa and in nasal polyps

BACKGROUND: The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. METHODS: Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3'OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. RESULTS: We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti-Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. CONCLUSION: The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.     

β-连环素及Notch1蛋白质在鼻内翻性乳头状瘤中的表达及意义

目的通过对鼻内翻性乳头状瘤（nasal inverted papilloma,NIP）组织中β-连环素（β-catenin）及Notch1表达水平的测定,探讨NIP中Wnt及Notch信号传导系统的调控作用。方法63例鼻内翻性乳头状瘤、30例鼻息肉、38例鼻腔鼻窦鳞状细胞癌（简称鳞癌）及11例正常鼻黏膜组织均采用免疫组织化学法检测β-catenin及Notch1蛋白质的表达水平。结果鼻息肉、鼻内翻性乳头状瘤和鼻腔鼻窦鳞癌中的β-catenin异常表达率分别为3.33%、58.73%和78.95%;正常鼻黏膜、鼻息肉、鼻内翻性乳头状瘤和鼻腔鼻窦鳞癌中Notch1阳性表达率分别为27.27%、36.67%、73.02%和92.11%,呈阶梯状升高且差异有统计学意义（P〈0.05）;β-catenin异位表达与鼻内翻性乳头状瘤不典型增生程度有一定的相关性（P〈0.05）,复发组中Notch1的水平明显高于初发组（P〈0.05）。结论Wnt/β-catenin和Notch信号途径的异常激活对NIP中起不同作用,β-catenin对NIP的发生发展及最终恶变成鳞癌可能起到了重要作用,术后Notch1水平升高可提示NIP复发。     

Jab1和p27kip1基因在喉鳞状细胞癌组织和喉癌Hep-2细胞中的表达及意义

目的:探讨Jab1和p27kip1基因在喉鳞状细胞癌组织和喉癌Hep-2细胞中的表达及意义。方法:采用免疫组织化学方法检测50例喉鳞状细胞癌组织和10例癌旁正常组织中Jab1和p27kip1的表达。采用人工合成Jab1siRNAⅡ用脂质体2000包裹后转染Hep-2细胞,用RT-PCR方法分析转染后喉癌细胞中Jab1和p27kip1基因的表达情况。结果:Jab1和p27kip1蛋白的阳性表达定位为细胞核中,Jab1在人喉鳞状细胞癌组织中高表达,正常喉黏膜中不表达或弱表达;p27kip1在人喉癌组织中弱表达,正常喉黏膜中强表达;两者呈负相关。Jab1siRNAⅡ可降低Jab1mRNA表达,并且随着时间的延长,Jab1mRNAⅡ在Hep-2细胞中的表达逐渐减弱,而p27kip1 mRNA的表达则无明显变化。结论:Jab1在人喉鳞状细胞癌组织中表达增强,正常喉黏膜中不表达或弱表达;p27kip1则正好相反。两者在喉癌中的表达呈负相关。Jab1siRNAⅡ可以特异性降低Jab1mRNA在喉癌Hep-2细胞中的表达,为进一步研究Jab1基因在喉癌中的作用奠定了基础。     

Human papillomavirus (HPV) in sinonasal papillomas: A study of 78 cases using in situ hybridization and polymerase chain reaction

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.     

鼻腔鼻窦内翻性乳头状瘤CEA及AgNOR表达的临床意义

为探索预测鼻内翻性乳头状瘤（NIP）癌变的可能性，采用免疫组化ABC法及胶银染色技术分别对20例NIP共24份标本进行CEA及AgNOR检测，以16例鼻息肉及18例界窦鳞癌为对照组。结果在20例NIP中有4例NIP术后切除大标本局部癌变，而术前标本示不典型增生。在此8价标本中（术前4份，术后4份），CEA全部呈浆膜型阳性，与鼻窦鳞癌CEA表达类型一致。AgNOR计数，术前标本与术后癌变标本其AgNOR颗粒分别为5．83个与8．86个，两者有显著差异，且术前标本AgNOR计数与其它3例不典型增生NIP均属同一组。结论，CEA在NIP中表达的类型在预测NIP癌变的临床应用上比AgNOR计数更有价值。     

Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses

Nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma. To determine the etiological role of human papillomavirus in inverted papilloma, and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor, we retrospectively analyzed inverted papillomas from 26 patients, 7 of whom had squamous cell carcinoma. We used an immunohistochemical method and molecular pathologic techniques, or dot-blot hybridization of DNA extracted from paraffin-embedded tissues, in situ hybridization, and polymerase chain reaction. Human papillomavirus was detected in 5 of 26 patients (19%), 3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16. The latter 2 patients had inverted papillomas associated with squamous cell carcinoma. We speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas.