Immunohistochemical Study Of P53 Research Articles

PS02.090: WHY BARRETT’S ESOPHAGEAL ADENOCARCINOMAS WERE FOUND AS WIDE LESIONS

Abstract Background Barrett's esohageal adenocarcinoma(BEA) originated from Long-segment Barrett's esophagus(LSBE) were found to be larger lesions than BEA from Short-segment Barrett's esophagus(SSBE). In Japan, superficial BEA were found and treated by ESD. However, most of superficial BEA in Japan are originated from SSBE. We investigated about the differences between BEA from SSBE and LSBE. Methods We examined macroscopic appearance and histology for superficial BEA. And we compared with BEA between SSBE and LSBE.And then we examined imminohistochemical study using p53 for operated specimens of superficial BEA. Results The multiple lesions were presented only LSBE cases. Operations were the far more common treatment for LSBE. The ratio of lesions involving more than one-half of the lumen was significantly larger in LSBE cases. The percentage of type 0-IIb was only 3.2%(3/95) for SSBE, whereas 32.6%(15/46) for LSBE (P < 0.05). When we placed each macroscopic type into one of two groups (Elevated and Flat or depressed type), we found that elevated types accounted for 63.2%(60/95) in SSBE cases. In LSBE cases, 50.0%(23/46) were of the flat or depressed type. In SSBE, simple macroscopic types accounted for 69.5%(66/95). Whereas, in LSBE cases, 50.0%(23/46) were of complex macroscopic types (P < 0.05). The lesions with accompanied type 0- IIb accounted for 2.1%(2/95) of SSBE and 21.7%(10/46) of LSBE(P < 0.05). The more common macroscopic type of T1b invasion was type 0- IIa + IIc. p53 immunohistochemical study was done for an operated specimen. This case was operated for superficial BEA. p53 was strongly positive on adenocarcinoma. However, we could find p53 strongly positive part on other part of the specimens. There were three part of p53 positive are in this operated specimens. These parts were not defined adenocarcinoma by HE stained. Conclusion Most superficial BEA originated from SSBE could be distinguished by the elevated lesions. Whereas, in cases of LSBE, flat type lesions including the accompanied type 0- IIb and multiple lesions, operation cases, the ratios of lesions involving a large range and the complex macroscopic types were significantly higher. When we diagnose and treat superficial BEA, it is necessary to consider the differences between SSBE and LSBE, such as macroscopic types. Disclosure All authors have declared no conflicts of interest.

Soft Tissue Recurrence with a Mucocele of an Intraosseous Ameloblastoma

Ameloblastoma is an odontogenic tumor of high frequency and usually occurs as an intraosseous growth. Ameloblastomas frequently recur, sometimes undergoing malignant transformation. These tumors are usually characterized as being multilocular, of the follicular type histopathologically, and invading strongly at the border region of the tumor. More than 10% p53-positive tumor cells give a prognostic indication for a tendency to recur. A recurrent ameloblastoma usually occurs in the intraosseous region near the site of the original lesion. In very rare cases, a recurrent tumor proliferates distantly from the original site in the soft tissue only. We report a rare case of recurrent ameloblastoma in the buccal mucosa with a mucocele that originated from the small salivary glands after the extirpation of an intraosseous (mandibular) ameloblastoma. We also performed a p53 immunohistochemical study of this recurrent tumor.

P53 as a prognostic marker associated with the risk of mortality for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is often associated with a poor prognosis. The purpose of the present study was to investigate survival and the risk of mortality in OSCC with regard to stage, tumor site and p53 expression. A retrospective study was performed on 150 non-consecutive cases of OSCC that were observed between January 1992 and January 2012, and were selected from a total of 580 patients according to the criteria of the homogeneity of histopathological grading (G2). The medical records were reviewed for 48 cases with disease at stage I [37 males, age 64.7±5.7 years (mean age±standard deviation); 11 females, age 70.0±3.37 years]; 27 cases with stage II (15 males, age 64.5±5.6 years; 12 females, age 69.2±3.9 years); 58 cases with stage IVa (42 males, age 66.9±5.3 years; 16 females, age 64.2±6.5 years); and 17 cases with stage IVb (16 males, age 65.7±5.4 years; 1 female, age 69 years). Monoclonal p53 antibody (clone DO-7) was used to perform the p53 immunohistochemical study. A significant association was found between the site of the tumor and p53 overexpression (P<0.0001). Stage I-II cases showed a higher cumulative probability of a 24-month survival time than stage IVa-IVb cases (P<0.0001). Cheek, floor and soft palate tumors showed a worse prognosis (P<0.0001) and tumors with p53 overexpression >50% showed a poor survival rate (P<0.0001) compared with tumors of the attached gingiva, tongue and retromolar trigone. The findings allowed the quantification of the risk mortality from OSSC with regard to stage, tumor site and the p53 expression pattern of the tumor. Data supported the absolute indications for wide surgical margins (radical surgery) in cases of T1-T2 N0 tumors of the tongue, floor, retromolar trigone and attached gingiva when p53 overexpression is >50% in association with a higher risk of mortality compared with when p53 overexpression is <50%.

Immunohistochemical study of p53, Ki-67, epidermal growth factor receptor, and sex-determining region Y-box 2 in squamous cell carcinoma of tongue

Objective: Tongue cancer (TC) is one of the most common oral cancers. Prognostic evaluation of this tumor includes histologic grade and TNM stage. In this study, we evaluated the expression of p53, Ki-67, epidermal growth factor receptor (EGFR), and sex-determining region Y-box 2 (SOX2) and correlated it with the clinicopathologic variables to assess their potential for use as prognostic markers. We compared the p53 positive and negative group. Design: A retrospective and prospective study with 45 cases of biopsy proven TC which were studied for the expression of p53, Ki-67, EGFR, and SOX2. The results were correlated with known clinicopathologic variables using Chi-square test. The p53 positive and negative groups were compared. Materials and Methods: Archieved blocks of biopsy proven TC were retrieved. Using 4 micron sections of the blockes immunostaining for p53, Ki67, EGFR and SOX2 was done. Results: P53 expression was 68.9%, Ki-67 was 88.9%, EGFR was 48.9%, and SOX2 was 35.6%. Expression of p53 and Ki-67 did not show any correlation with any of the clinicopathologic variables. There was a statistically significant association between EGFR expression and lymph node (LN) positivity (P = 0.001). Stage of tumor and SOX2 positivity showed a significant correlation (P = 0.03). The comparison of p53 positive and negative groups did not reveal a significant difference. Conclusion: p53-negative TC is not significantly different from the p53-positive TC at presentation. The absence of mutant p53 in more than 30% TC points toward the possible etiological role of human papillomavirus in TC. Larger studies are needed to evaluate the possible use of EGFR for prediction of LN metastasis and SOX2 as a prognostic marker.

Effect of hesperidin on mice bearing Ehrlich solid carcinoma maintained on doxorubicin.

Doxorubicin (DOX) is widely used in cancer therapy of many carcinomas types. Unfortunately, DOX is not sufficiently effective in many cases, and increasing the dosage of it is limited due to its systemic toxicity. A citrus flavonoid hesperidin (HES) is proved to be potent antioxidant and protective agent against many diseases including cancer. In this context, the objective of this study was to examine effect of HES along with DOX on solid Ehrlich carcinoma (SEC) in mice. Forty male mice were divided into four equal groups (n = 10): control SEC, DOX, HES, and DOX + HES. HES (50 mg/kg body weight orally) was given day after day for 16 days along with DOX (4 mg/kg body weight i.p. injection) for 5 cycles every 4 days in ESC-inoculated mice. After 20 days, tumor volume, tumor weight, survival rate, tumor glutathione, nitric oxide content, and serum glutathione were determined. Tumor tissue was examined for histopathological and immunohistochemical study for p53 and VEGF. Tumor resistance for mdr1a gene was assessed in tumor tissue by RT-PCR. HES induced significant increase in tissue and serum glutathione with significant decrease in tumor volume and tumor weight. A possible role of HES to modulate gene expression of mdr1a in tumor tissue was established. In addition, HES alleviated the histopathological changes with significant decrease in p53 and VEGF expression. The use of HES as adjuvant therapy with DOX would enhance the therapeutic efficacy and alleviate the resistance to DOX in treatment of solid tumors.

Immunohistochemical study of p53, Ki-67, Bax and Bcl-2 in diethylnitrosamine induced hepatocarcinogenesis in rats treated withCassia fistulaleaf extract

Immunohistochemical study of p53, Ki-67, Bax and Bcl-2 in diethylnitrosamine induced hepatocarcinogenesis in rats treated with<i>Cassia fistula</i>leaf extract

Effect of Green Tea Extract on the Interferon-Induced Testicular Apoptosis in the Adult Albino Rat: Immunohistochemical and Electron Microscopic Study

Background: Interferons (IFNs) are widely used in the treatment of various diseases and can disrupt spermatogenesis and inhibition Leydig cell steroidogenesis through the formation of reactive oxygen species (ROSs) that cause oxidative stress. Aim of the work: In this study we examine the effect of (IFN) on rat spermatogonia and investigate the possible protective effect of Grean tea on (IFN)-induced spermatogonia appotosis. Material and Methods: Forty-eight adult male albino rats (240-280 g) were used in this study. They were divided into three groups. Group I in which rats were served as a control and were given sterile normal saline. The rats in Group II were given 7.500 units of interferon (INF) α-2β, considered in clinical treatment dose range, 3 times weekly under inhalation anesthesia for 2 month (Group II a) and 3 month (Group II b). Group III received Green tea extract and interferon α-2β in the same dose of group (II) for 2 month (Group III a) and 3 month (Group III b). 200 mg of green tea extract was dissolved in distal water and solution was administrated orally through gastric tube at dose level of (40 mg/k.g.b.w.). At the end of the 2 and 3 month respectively, bilateral orchiectomy was performed through standard ilioinguinal incisions and the rats were sacrified by pentobarbital overdose (200 mg=kg) inhalation. The testes were removed and separated. A part of one testis was fixed in Bouin fixative to be used for histopathological and immunohistochemical studies for p53 and the other part was used in a fresh state to determine the level of the Superoxide Dismutase (SOD). The other testis was fixed in 1% gluteraldehyde and 4% formaldehyde in (pH 7.4) for at least 2 hours to overnight. Ultrathin sections processed for transmission electron microscopic studies. Results: Interferon induced testicular damage that is revealed by loss of testicular architecture through Hx. and E. stained sections, Immunohistochemical stained sections against p53 and the electron microscopic examination. These findings were accompanied by significant reduction in diameter of seminiferous tubules and thickness of the germinal epithelium with significant reduction in SOD. Otherwise, the green tea extract definitely reverse the above mentioned findings with improvement of testicular architecture and significant increase in diameter of seminiferous tubules, thickness of the germinal epithelium and elevated SOD. The mean of the diameter of the seminiferous tubules of Group IIa showed a significant decrease by nearly 34% in comparison to Group IIb showed a higher significant decrease by nearly 43%. The mean of the thickness of the seminiferous tubules of Group IIa showed a significant reduction by nearly 33% while in Group IIb showed a higher significant reduction by nearly 50%. The mean of the level of the Superoxide Dismutase in Group IIa showed significant decrease by nearly the half while in Group IIb revealed a higher significant decrease by nearly 59%. The mean of the diameter of the seminiferous tubules in Group IIIa showed a significant increase by nearly 32% and by nearly 43% in Group IIIb. The mean of the thickness of the seminiferous tubules in Group IIIa showed significant increase by nearly 11% while in Group IIIb the significant increase was by nearly 45%. The mean of the level of the Superoxide Dismutase of the seminiferous tubules in Group IIIa did not show significant increase while in Group IIIb revealed a higher significant increase by nearly 48% Group IIIb. Conclusion: The green tea extract has a powerful antioxidant effect that can reverse the damage caused

Immunohistochemical study of p53 and proliferating cell nuclear antigen expression in odontogenic keratocyst and periapical cyst

Introduction:p53 protein is a product of p53 gene, which is now classified as a tumor suppressor gene. The gene is a frequent target for mutation, being seen as a common step in the pathogenesis of many human cancers. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and plays a critical role in initiation of cell proliferation.Aim:The aim of this study is to assess and compare the expression of p53 and PCNA in lining epithelium of odontogenic keratocyst (OKC) and periapical cyst (PA).Materials and Methods:A total of 20 cases comprising 10 OKC and 10 PA were included in retrospective study. Three paraffin section of 4 μm were cut, one was used for routine hematoxylin and eosin stain, while the other two were used for immunohistochemistry. Statistical analysis was performed using Chi-square test.Results:The level of staining and intensity were assessed in all these cases. OKC showed PCNA expression in all cases (100%), whereas in perapical cyst only 60% of cases exhibited PCNA staining. (1) OKC showed p53 expression in 6 cases (60%) whereas in PA only 10% of the cases exhibited p53 staining. Chi-square test showed PCNA staining intensity was more significant than p53 in OKC. (2) The staining intensity of PA using p53, PCNA revealed that PCNA stating intensity was more significant than p53.Conclusion:OKC shows significant proliferative activity than PA using PCNA and p53. PCNA staining was more intense when compared with p53 in both OKC and PA.

Immunohistochemical study of p53, Ki-67, MMP-2 and MMP-9 expression at invasive front of squamous cell and verrucous carcinoma in oral cavity

Squamous cell carcinoma (SCC) is the most common malignancy in the oral cavity. Verrucous carcinoma (VC) is a lower grade subtype of SCC with pathological similarities but different management. Tumor invasive front (TIF) is a dynamic location in the differentiation of malignancies. p53 is a tumor suppressor and Ki-67 a proliferation marker. Matrix metalloproteinases 2 and 9 are involved in the tumor invasiveness. We assessed these markers in TIF of oral SCC and VC to find more precise grading scales.We studied the expression of markers in the invasive front of 42 cases of SCC (21 high and 21 low grade), 20 cases of VC and 8 cases of normal oral mucosa using immunohistochemistry.There were significant differences among the study groups regarding the number of cells expressing p53, MMP-2 and 9.Except for Ki-67, other studied markers can be used for the histological grading of SCC and its differentiation from VC. MMP-9 is the most reliable one for invasive SCC grading. The extent of the expression of these markers is related to the infiltration pattern of SCC at the invasive front. The less invasive nature of VC can be associated with the expression pattern of these markers.

Head and Neck Large Cell Neuroendocrine Carcinoma Should Be Separated From Atypical Carcinoid On the Basis of Different Clinical Features, Overall Survival, and Pathogenesis

According to the 2005 World Health Organization classification of head and neck tumors, neuroendocrine tumors can be subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma. Similar tumors diagnosed as large cell neuroendocrine carcinomas (LCNECs) in the lung are diagnosed as atypical carcinoids in the head and neck region. We studied neuroendocrine tumors and analyzed whether LCNEC should be separated from atypical carcinoid in the head and neck region. Twenty-three cases of primary head and neck neuroendocrine tumors were included and subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma according to the 2005 World Health Organization guidelines, and then LCNECs were separated from atypical carcinoids according to modified criteria using the Ki-67-labeling index and mitotic count. Clinical information and survival data were obtained, and immunohistochemical studies for p53 were conducted. The 5-year survival rates for the 2 typical carcinoids, 7 atypical carcinoids, 7 LCNECs, and 7 small cell carcinomas were 100.0%, 83.3%, 21.4%, and 20.8%, respectively (P=0.032). The LCNEC patients were older (mean age, 61 vs. 41 y; P=0.038), more commonly in advanced stage (stages III and IV 100% vs. 28.6%, P=0.01), with a poorer prognosis (5-year survival 21.4% vs. 83.3%, P=0.03), and more commonly had tumors overexpressing p53 (85.7% vs. 0%, P=0.005) as compared with atypical carcinoid patients. LCNECs should be separated from atypical carcinoids as a new entity of neuroendocrine carcinoma in the head and neck region. The new classification may provide better risk stratification and useful information for proper treatment.

Expression of Molecular Markers in the Tumor and Survival Prognosis in Osteosarcoma

Immunohistochemical study of p53, VEGF, Flt-1/VEGFR1 Ab-1, EGFR, HER-2/neu, Bax, and Cox-2 expression in osteosarcomas was carried out in 40 patients aged 16-70 years. Expression of p53 was detected in 27.5% tumors, VEGF in 15%, Flt-1/VEGFR1 Ab-1 in 97.5%, EGFR in 52.5%, HER-2/neu in 32.5%, Bax in 77.8%, and Cox-2 in 32.3% tumors. Multifactorial analysis showed that the expression of HER-2/neu (p=0.004), p53 (p=0.01), and Cox-2 (p=0.04) in osteosarcomas significantly correlated with unfavorable prognosis for overall survival, while HER-2/neu (p=0.02) and Cox-2 (p=0.003) with relapse-free survival. Analysis of HER-2/neu, p53, and Cox-2 expression in the primary tumor should be taken into consideration in the treatment of patients with osteosarcoma.

Esophageal Small Cell Carcinoma

Abstract Objective.—To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma. Method.—Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made. Results.—Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810–964) positive cells per 1000. Overall median survival was ...

Gynaecological cancers in genetically susceptible women: new thoughts on tubal pathology

Women may be genetically susceptible to development of gynecological cancers. Major familial ovarian cancer syndromes include site-specific ovarian cancer, breast/ovarian cancer, and hereditary non-polyposis colon cancer (HNPCC). The former two syndromes are linked to BRCA1 and BRCA2 genes while DNA repair genes such as hMSH2 and hMLH1 are commonly involved in HNPCC. Carriers are also prone to endometrial carcinoma. BRCA mutation related ovarian tumours are more likely to be high grade serous whilst borderline tumours are conspicuously absent. Papillary serous carcinomas of the peritoneum and fallopian tube are also reported. In recent years, serous tubal intraepithelial carcinoma and transitional metaplasia, its mimick, are identified at the fimbria of prophylactic salpingo-oophorectomy specimens. Immunohistochemical studies for p53 and MIB1 may help in the diagnosis. Tubal pathology is also occasionally reported in Peutz-Jeghers syndrome. Such findings emphasize on the importance of careful pathological examination of the fallopian tube in genetically susceptible women.

Immunohistochemical study of p53 and angiogenesis in benign and preneoplastic oral lesions and oral squamous cell carcinoma

Mutation of the p53 gene and overexpression of its protein are frequent in human cancer, suggesting that these events play a critical role in the onset or progression of many types of tumors. Angiogenesis also has been demonstrated to be associated with tumor progression, aggressiveness, and metastases. This study aimed to investigate-in normal oral epithelium, hyperplasia, dysplasia, and invasive oral squamous cell carcinoma-the prevalence of p53 protein immunoreactivity and of angiogenesis, and to determine the correlation between them. The study was performed on tissue sections of hyperplasia (n = 14), dysplasia (n = 10), and invasive squamous cell carcinoma (n = 21). Seven normal samples of oral mucosa were used as control. Angiogenesis and p53 protein expression were investigated by means of immunohistochemistry. This study showed that p53 protein was confined to the basal cell layer in normal oral mucosa and in the hyperplastic group. In the dysplastic group, it was expressed in the basal and suprabasal layer, whereas in invasive carcinoma, it was detected in central and peripheral regions. The percentage of p53-positive cells was evaluated, and statistically significant differences were found between normal oral mucosa and severe dysplasia, between normal mucosa and invasive carcinoma, and between mild and severe dysplasia. p53 expression showed no significant correlation with tumor grading. Angiogenesis was assessed using the endothelial cell marker von Willebrand's factor. The number and size of blood vessels increased from normal oral epithelium through dysplastic epithelium to reach a maximum in invasive carcinoma. Angiogenesis and p53 protein immunoreactivity increased with progression from normal mucosa to invasive carcinoma, and both factors were directly correlated to each other suggesting that they may play a critical role in oral carcinogenesis.

Immunohistochemical study of p53, c-erbB-2, and PCNA in barrett's esophagus with dysplasia and adenocarcinoma arising from experimental acid or alkaline reflux model.

An immunohistochemical study of p53, c-erbB-2, and proliferating cell nuclear antigen (PCNA) in Barrett's esophagus with dysplasia and adenocarcinoma, arising from experimental acid or alkaline reflux, was performed in dogs. Cardiectomy was performed in group A (n = 26) as an acid reflux model, and total gastrectomy was performed in group B (n = 24) as an alkaline reflux model. After surgery, the esophageal mucosa was observed and biopsied endoscopically every 3 months over a period of 6 years. Immunohistochemical staining of p53. c-erbB-2, and PCNA was performed, using biopsied specimens. In group A, Barrett's esophagus developed in 14 of the 26 dogs. Low-grade dysplasia occurred in 5 of the 26 dogs, and in 1 of these 5 dogs, it developed into high-grade dysplasia. In this animal, adenocarcinoma arose 63 months after the operation. In group B, Barrett's esophagus developed in 10 of the 24 dogs. Low-grade dysplasia was observed in 4 of the 24 dogs. In 1 of these 4 dogs, the dysplasia became high-grade and adenocarcinoma occurred 66 months after the operation. In group A, PCNA was positive in adenocarcinoma; the PCNA labeling index (LI) was 58. c-erbB-2 and p53 were negative in all animals in group A. In group B, PCNA was positive in Barrett's esophagus with high-grade dysplasia and adenocarcinoma; the PCNA LI was 77. p53 was positive in adenocarcinoma. c-erbB-2 was negative in adenocarcinoma. CONCLUSIONS; The results of this study provided evidence of the dysplasia-carcinoma sequence arising from alkaline reflux, as well as from acid reflux. To the best of our knowledge, this is the first report of the use of an alkaline reflux model and a 6-year study using dogs to observe the course of Barrett's esophagus.

P53 and hMSH2 expression in basal cell carcinomas and malignant melanomas from photoexposed areas of head and neck region

Ultraviolet (UV) radiation plays a pivotal role in skin damage and photocarcinogenesis. The basic mechanism of phototoxicity lies in DNA damage, and involves mutation of tumor suppressor genes, oncogenes and genes directly involved in the control of the stability of genome, such as the mismatch repair (MR) genes. The goal of this study was to evaluate the role of p53 and hMSH2 in the UV-related carcinogenetic process. An immunohistochemical study for p53 and hMSH2 was performed in a series of 43 basal cell carcinomas (BCC) and 60 melanomas (MM) from photoexposed areas of head and neck region, comparing the findings with follow-up. A deregulated p53 expression characterized less differentiated, more aggressive BCC (BCC2) but not the well-differentiated ones (BCC1). The hMSH2 protein was present, though expressed at varying levels, in 18 out of 21 BCC1 cases and in 4 out of 22 BCC2. In the remaining 3 cases of BCC1 and 18 cases of BCC2, a complete absence of hMSH2 expression was found, correlating directly with the presence of recurrence and/or death of the disease in case of melanoma (p<0.05). Overall, the expression of hMSH2 correlated inversely with the p53 overexpression (p<0.01). In MM, p53 was found overexpressed in 81.6% of the cases, and this correlated positively with the level of infiltration and with the presence of relapses (p<0.01) or metastasis (p<0.01) and inversely with the disease-free interval (p<0.05). These results are in agreement with the reported association between p53 deregulation and a more aggressive cancer phenotype. The evaluation of the expression of p53 and hMSH2 could improve the management of patients with BCC and MM, and could have a role also in the evaluation of the early cutaneous photo-inducted damage, contributing to the identification of presymptomatic patients predisposed to the development of UV-related new skin tumors, who could become candidates for chemoprevention trials.

Immunohistochemical study of p53, p21 and PCNA in pterygium

Since mutated p53 is one of the most frequent gene abnormalities in human cancer, we hypothesized that mutation of p53 may play an important role in growth and recurrence of pterygia, a dysplasia of the conjunctiva. Therefore, we compared pterygia of Japanese and Tunisian patients using antibodies against p53, p21 and proliferating cell nuclear antigen (PCNA). In Nagasaki, 21 pterygia of Japanese individuals were removed and in Gabes, 19 primary pterygia of Tunisian individuals. Positive staining of wild type p53 was not found in the Japanese pterygia, whereas 38.1% were positive for mutant p53, none were positive for p21 and 76.2% were positive for PCNA. The incidence of mutant p53-positive staining was 50.0% in males and 22.2% in females, which was statistically significant. In the 19 Tunisian patients, positive staining of wild type p53 was not found, whereas 36.8% were positive for mutant p53, 0% for p21 and 63.1% for PCNA. Differences between Japanese patients and Tunisian patients were not significant. There were 2 types of pterygium. One type did not show mutant p53 and the other showed mutant p53 caused by ultraviolet light. However, damage caused by p53-dependent programmed cell death of pterygium cells may lead to mutations in other genes which may allow the progressive multistep development of limbal tumors. It is possible that mutant p53-positive pterygia can develop into limbal tumors.

Esophageal small cell carcinomas: clinicopathologic parameters, p53 overexpression, proliferation marker, and their impact on pathogenesis.

To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma. Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made. Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810-964) positive cells per 1000. Overall median survival was 3.4 months. In patients who underwent chemotherapy, there was significant response. Esophageal small cell carcinoma is an aggressive tumor. Overexpression of p53 is associated with early stages of carcinogenesis. The high proliferative index, as defined by the MIB-1 immunohistochemical method, may be related to aggressive behavior and high sensitivity to chemotherapy and radiotherapy.

Immunohistochemical and mutational analysis of p53 tumor suppressor gene in gestational trophoblastic disease: correlation with mdm2, proliferation index, and clinicopathologic parameters.

The role of p53 in the pathogenesis of gestational trophoblastic disease (GTD) was investigated. Immunohistochemical studies for p53, its regulator mdm2, and proliferation marker Ki67 were performed on paraffin-embedded tissues of 28 partial moles (PM), 57 complete moles (CM), 14 choriocarcinomas (CCA), and 31 normal placentas. Three antibodies to p53 (DO-7, Ab-2, Ab-3) were used and demonstrated immunoreactivity for wild-type p53 protein predominantly in the nuclei of cytotrophoblasts. Direct DNA sequencing of 36 hydatidiform moles using frozen tissues confirmed an absence of mutational changes in exons 5-8. CCA was found to have the highest p53 protein expression, followed by CM, PM, and normal placenta (P < 0.001). In normal placentas (P = 0.0001), PM, and CM (P = 0.016), an inverse correlation between their gestational age and p53 expression was observed. p53 expression was found to correlate with proliferation index in normal placenta (P = 0.0001) and all three groups of GTD (P = 0.012). Significant correlation between p53 and mdm2 expression was also observed (P < 0.01). The distinctive expression of p53 wild-type protein in the cytotrophoblasts and its positive correlation with the proliferative index suggests that its overexpression in GTD may be related to its effect on cell proliferation. The parallel expression of mdm2 and p53 also supports the presence of an autoregulatory feedback loop in the control of this process. No correlation could be found between clinical progress of the patients with hydatidiform moles, and the p53 (P = 0.78) or mdm2 protein (P = 0.54) expression suggesting that neither of them carries any prognostic significance.

An immunohistochemical study of p53 and PCNA in inflammatory papillary hyperplasia of the palate: a dilemma of interpretation.

Inflammatory papillary hyperplasia of the palate (IPHP) or the granular type of denture stomatitis, is a non-neoplastic lesion characterized histologically by a significant epithelial hyperplasia and inflammatory infiltrate usually caused by trauma and Candida infection. p53 and proliferative cell nuclear antigen (PCNA) are cell-cycle regulators, that when overexpressed, are considered by many investigators as markers of malignant transformation. The objective of this study was to investigate the immunodetection of p53 and PCNA in IPHP, and to correlate these results with the degree of epithelial hyperplasia and inflammatory infiltrate. In 12 cases diagnosed clinically as IPHP, Candida was cultured from the denture base and the palatal mucosa. Lesions were biopsied and stained with H&E for histomorphometric analysis of the epithelial width and inflammatory infiltrate. PAS and Gram stains were used for screening of Candida. Sections were immunostained with DO-7 for p53 and PC-10 for PCNA. Fifteen palatal biopsies obtained from autopsies of edentulous subjects with normal palatal mucosa served as controls. All cultures of swabs from both the palatal mucosa and denture base were positive for Candida. Candidal hyphae could not be identified in PAS stained sections. Small foci of Gram-positive organisms were found in two cases of IPHP. Epithelial width and inflammation were significantly higher in IPHP than in controls (P < 0.001). A three-fold increase in positively stained cells for p53 and a two-fold increase in positively stained cells for PCNA were seen in IPHP compared with controls (P < 0.001). Although a significant increase in the immunodetection of p53 and PCNA may indicate a malignant potential, IPHP has never been reported to undergo malignant transformation nor is it associated with cytologic signs of dysplasia. The increase in the epithelial width and inflammation degree is probably associated with the colonization of the denture bases with Candida organisms. The increased detection of p53 and PCNA can be a secondary effect of cytokines originating from both the inflammatory cells and the keratinocytes. Thus, immunodetection of p53 and PCNA by current immunohistochemical methods on archival tissues is neither specific nor sensitive enough to be used as indicators for malignant potential in the absence of cytological dysplastic changes or genetic proof of mutated cell cycle genes.