Frequency Of P53 Overexpression Research Articles

P53 Over Expression in Bladder Carcinoma

Objective: The purpose of this research was to find out how prevalent p53 overexpression is in bladder urothelial cancer. Methodology: This descriptive, cross-sectional study was conducted in KRL Hospital Islamabad from April 2018 to October 2018. All patients with biopsy-proven urinary bladder cancer, irrespective of gender or age range, were included in the research. Non-probability, consecutive sampling technique was used. The immunohistochemical processing was completed, and the results for p53 expression (positive/negative) were interpreted by the consultant pathologist. SPSS version 22.0 was used for the statistical analysis. Quantitative information, such as the patient's age and length of illness, were displayed using the mean and standard deviation. The P value was less than 0.05, the result was declared significant. Results: The participants in this study ranged in age from 15 to 70 years old, with a mean age of 47.39 ± 10.26 years. The male to female ratio was 1.6:1 among these 74 patients, with 45 (60.81 percent) being male and 29 (39.19 percent) being female. Overexpression of p53 was found in 31 (41.89 percent) of bladder urothelial carcinoma cases. Conclusion: This study concluded that the frequency of p53 overexpression in bladder urothelial carcinoma is very high.

Clinicopathologic features and BRCA mutations in primary fallopian tube cancer in Japanese women.

The present study aimed to clarify the clinicopathological features, including the level of p53 protein expression and BRCA mutations, of primary fallopian tube cancer (PFTC) in Japanese women. A multicenter clinical survey was conducted at three Japanese institutions. Clinical data in patients with PFTC between 1998 and 2016 were collected. Immunohistochemical staining of p53 and BRCA mutation analysis by exome sequence using paraffin-embedded surgical resected specimens were performed. A total of 40 patients with PFTC were enrolled in the study. The median age was 58 years (range: 38-78 years); 31 patients were menopausal. Thirty-four (85.0%) patients were diagnosed with serous adenocarcinoma (high grade, 33; low grade, 1). PFTC was classified into ampulla type, fimbriae type and undeterminable type by tumor-occupying lesion; ampulla type and fimbriae type occurred with the same frequency. Among 30 patients with high-grade serous adenocarcinoma, 6 patients showed germline mutations of BRCA1 (stop-gain 4 and frameshift deletion 2) and 2 patients showed germline mutation of BRCA2 (stop-gain 1 and frameshift deletion 1). However, only 1 patient had familial history of breast or ovarian cancer. Patients with BRCA mutations in the germline were frequently observed in ampulla type and FIGO stage I/II cancers, but no significant difference in the frequency of p53 overexpression and overall survival was observed. Among Japanese patients with PFTC, 26.7% presented with BRCA mutations in the germline. Additionally, p53 was important for the carcinogenesis in fallopian tubes, independent of the specific BRCA mutation.

Clinical outcome and molecular characterization of pediatric glioblastoma treated with postoperative radiotherapy with concurrent and adjuvant temozolomide: a single institutional study of 66 children.

Glioblastoma (GBM) in children is rare. Pediatric GBM have a distinct molecular profile as compared to adult GBM. There are relatively few studies of pediatric GBMs and no standard of care on adjuvant therapy. We aimed to evaluate the clinical outcome and molecular profile of pediatric GBM. Between 2004 and 2013, 66 consecutive children with histologically proven GBM were identified from our database. The majority of the children underwent maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolomide. Immunohistochemical staining was performed for p53, MIB-1 labeling index, MGMT overexpression, and EGFR amplification and isocitrate dehydrogenase (IDH1) R132H point mutation. Survival and impact of possible prognostic factors on outcomes were analyzed. Median survival was 15 months. The overall survival rate at 1 year was 62%, at 2 years was 30%, and at 3 years was 27%. Patients with thalamic tumors (P < .001), incompletely resected tumors (P < .00001), and tumors with MIB-1 labeling index >25% (P < .002) had poor overall survival rates. p53 was overexpressed in 74% of patients, MGMT promoter methylation was seen in 37% of patients, IDH1 mutation was seen in 4% of patients, and no patients had EGFR amplification. MGMT methylation and p53 overexpression did not impact survival. Clinical outcome of pediatric GBM is similar to that reported for adult GBM. The frequency of p53 overexpression is higher than in adult GBM, while MGMT methylation, IDH1 mutations and EGFR amplification is lower than in adult GBM. MGMT methylation and p53 expression status do not have any prognostic significance.

Histomorphologic and Molecular Features of Pouch and Peripouch Adenocarcinoma

The occurrence of adenocarcinoma after ileal pouch-anal anastomosis for ulcerative colitis (UC) is an infrequent but potentially lethal complication. Neither histomorphologic nor molecular features of pouch adenocarcinoma after ileal pouch-anal anastomosis have been fully investigated. We report the largest series of 12 pouch and peripouch adenocarcinomas and compared them with 58 randomly selected UC-associated adenocarcinomas. The mean age of patients with pouch/peripouch adenocarcinoma was 55.2 years (SD 14.8), which was not significantly different from that of controls (P=0.52). Pouch/peripouch adenocarcinoma and UC-associated adenocarcinoma had a comparable frequency of tumor-infiltrating lymphocytes, lack of dirty necrosis, mucin differentiation, signet ring cell differentiation, heterogeneity, and well differentiation (P>0.05 for all). Pouch/peripouch adenocarcinoma was more likely to show Crohn-like reaction compared with UC-associated adenocarcinoma (P=0.047). Loss of at least 1 mismatch repair protein was noted in 9% of pouch/peripouch adenocarcinomas and 9.6% of UC-related adenocarcinomas (P=1.0). There was no significant difference in the frequency of p53 overexpression (36.4% vs. 61.1%, P=0.184) or nuclear immunoreactivity for β-catenin (9% vs. 7.4%, P=0.99) in pouch/peripouch versus UC-associated adenocarcinomas, respectively. Pouch/peripouch and UC-associated adenocarcinoma had a comparable positive rate for CK7 (54.5% vs. 55.5%, P=0.99), CK20 (100% vs. 98.1%, P=0.99), and CDX2 (72.8% vs. 72.2%, P=0.99) by immunohistochemistry. In summary, pouch and peripouch adenocarcinoma can occur in patients without colorectal neoplasia and in those with idiopathic inflammatory bowel disease, can be potentially lethal, and has histomorphologic and molecular features similar to those of UC-associated adenocarcinoma.

Low Frequency of Epstein Barr Virus Association and High Frequency of p53 Overexpression in an Argentinean Pediatric T-Cell Lymphoma Series

T-cell non-Hodgkin's lymphomas (NHLs) represent 10% to 15% of all diagnosed lymphomas in Western countries. Various geographic frequencies of T-cell NHL have been documented, in part reflecting increased exposure to pathogenic factors such as Epstein-Barr virus (EBV). Our aims were to assess EBV and p53 expression in Argentine pediatric T-cell lymphoma and to correlate them with patients' survival. Epstein-Barr encoded RNAs (EBERs) in situ hybridization and LMP1 and p53 immunohistochemical staining were performed on formalin-fixed paraffin-embedded lymph node biopsies from 25 pediatric T-lymphoma patients. In 17 of 25 samples good-quality DNA was obtained, and EBER polymerase chain reaction was assessed to confirm in situ hybridization and immunohistochemical results. Epstein-Barr virus expression was found in 8.0% of cases. p53-positive staining was distributed in 92% of pediatric cases. Kaplan-Meier survival analysis showed that neither EBV nor p53 expression was statistically significantly associated with event-free survival. Our data showed a low frequency of EBV association with pediatric T-cell lymphoma. It seems that p53 plays an important role in proliferation in our studied population, since it is overexpressed in 92% of T-cell lymphoma cases.

Lung adenocarcinoma with mixed bronchioloalveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization.

A significant proportion of small lung adenocarcinomas consists of two components: bronchioloalveolar carcinoma (BAC) and invasive carcinoma. The purpose of this study was to compare their clinicopathologic features with those of BAC and those of invasive cancer without BAC, and to define "early invasive" lesions based on the extent of invasive foci. We reviewed 484 lesions of resected lung adenocarcinoma and classified them into three groups according to tumor growth pattern: group 1 (n = 102, BAC), group 2 (n = 216, adenocarcinoma consisting of BAC and invasive carcinoma), and group 3 (n = 166, invasive adenocarcinoma without BAC component). Group 2 was further subdivided according to the extent of the invasive area: group 2a (n = 54), BAC with invasive foci <or=5 mm; group 2b (n = 162), BAC with invasive foci >5 mm. These groups were compared with regard to their clinicopathologic features, expression of Ki-67 and p53, and expression of laminin-5, a putative marker for tumor invasion. The positivity rates of vascular, lymphatic, and pleural invasion in each group were as follows: 0%, 0%, and 0% in group 1; 5.5%, 14.8%, and 1.9% in group 2a; 45.7%, 41.4%, and 25.9% in group 2b; and 84.9%, 61.4%, and 60.8% in group 3. Notably, no lymph node metastasis occurred in either group 2a or group 1, but it was observed in 24.1% of group 2b and 47.0% of group 3. The mean Ki-67 labeling index, the frequency of p53 overexpression, and the frequency of laminin-5 overexpression increased from group 1 (11%, 4%, and 0%) to group 2a (16%, 20%, and 7%) to group 2b (24%, 41%, and 23%) to group 3 (35%, 38%, and 38%). In contrast, no clear differences were observed when lesions were subdivided according to size. Based on the distribution pattern of Ki-67-positive tumor cells, lesions were classified into two groups: marginal type (63%) and nonmarginal type (37%). The latter showed a significantly higher labeling index than the former. Moreover, the proportion of the marginal type clearly decreased from group 1 (85%) and group 2a (87%) to group 2b (55%) to group 3 (19%). Group 2 lesions showed characteristics intermediate between the BAC and invasive adenocarcinoma. According to the extent of the invasive area, we were able to define a subgroup of mixed-type adenocarcinomas (group 2a) that could be regarded as early invasive cancer because they showed low rates of vascular, lymphatic, and pleural invasion, and no nodal involvement.

Improved survival in women with BRCA-associated ovarian carcinoma.

The objective of this study was to determine the clinical characteristics, treatment response, and frequency of p53 overexpression in Ashkenazi Jewish women with hereditary ovarian carcinoma. Seventy-one Jewish women with epithelial ovarian carcinoma (EOC) were tested for the three BRCA founder mutations using single-strand conformation polymorphism analysis, heteroduplex analysis, and protein truncation testing. Clinical and histopathologic data were reviewed retrospectively. In vitro chemoresistance was analyzed in 32 patients. Mutations of p53 were studied using immunohistochemical detection of p53 overexpression. Thirty-four of 71 Jewish patients with EOC (48%) had germline BRCA mutations (BRCA heterozygotes), including 22 BRCA1 mutations and 12 BRCA2 mutations. BRCA heterozygotes were younger compared with Jewish patients who had EOC without mutations (sporadic carcinoma; 50 years vs. 59 years, respectively; P = 0.01). BRCA1 heterozygotes were younger compared with BRCA2 heterozygotes (48 years vs. 57 years, respectively; P = 0.01). Histopathologic tumor features were similar; however, tumors with low malignant potential were seen only in women with sporadic carcinoma. Both groups had equivalent rates of surgical cytoreduction and similar median follow-up (72 months). BRCA heterozygotes had higher response rates to primary therapy compared with patients who had sporadic disease (P = 0.01). In vitro chemoresistance predicted tumor response to platinum chemotherapy correctly in BRCA heterozygotes (P = 0.0096). BRCA heterozygotes with advance-stage disease had improved survival compared with patients who had advanced stage sporadic carcinoma (91 months vs. 54 months, respectively; P = 0.046) and had a longer disease free interval (49 months vs. 19 months, respectively; P = 0.16). p53 overexpression was common in BRCA heterozygotes (80%). BRCA1 heterozygotes developed EOC at a younger age compared with BRCA2 heterozygotes and women who had sporadic ovarian carcinoma. BRCA heterozygotes had a better response to platinum chemotherapy compared with women who had sporadic disease, which may have contributed to their improved prognosis.

Colorectal carcinoma with special reference to growth pattern classifications: clinicopathologic characteristics and genetic changes.

Many colorectal carcinomas are known to develop from preexisting polypoid adenomas; however, they can also develop from so-called "flat adenomas". To elucidate the growth patterns of flat- or depressed-derived colorectal carcinomas, we investigated the clinicopathologic characteristics and genetic changes of invasive carcinomas. Seventy-five colorectal carcinomas were classified into three groups: 46 upward growth (UG) type, 22 downward growth (DG) type, and 7 lateral growth (LG) type. All of them had histologically infiltrated the submucosa (SM) and muscularis propria (MP). Ki-ras mutation was examined by polymerase chain reaction-single-strand conformation polymorphism analysis, and overexpression of p53 protein was analyzed by immunohistochemistry. No DG or LG carcinomas histologically demonstrated an adenomatous remnant, whereas UG carcinomas did (SM, 19 of 26; 73%; MP, 3 of 20; 15%). The percentage of tumors existing in the right colon was significantly higher in LG carcinomas (71%) than in the UG type (28%; P = 0.037). The frequency of Ki-ras mutation was significantly higher in the UG carcinomas than in the DG and LG carcinomas (52% vs 0%; P < 0.0001; and vs 0%; P = 0.014). However, the frequency of this mutation in SM-UG carcinomas with an adenomatous remnant (9 of 19; 47%) did not differ significantly from that in SM-UG carcinomas without an adenomatous remnant (3 of 7; 43%). The frequency of p53 overexpression did not differ among UG (57%), LG (57%), and DG (50%) carcinomas. These results suggest that UG carcinomas develop on the basis of the adenoma-carcinoma sequence, while the development of DG and LG carcinomas is different from that of UG carcinomas.

Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma.

An immunohistochemical analysis of over-expression of p53 and c-erbB-2 proteins was performed on 27 biopsies of laryngeal carcinoma. The aim of this study was to investigate whether there is a correlation between over-expression of these proteins and the clinicopathological features of the tumor and to reveal any possible prognostic value. Paraffin sections of laryngeal carcinoma were studied using immunohistochemical staining with mouse and rabbit monoclonal antibodies, respectively, for p53 and c-erbB-2 proteins. The positive controls were paraffin-embedded specimens from ten breast carcinomas previously shown to express these proteins. Ten benign laryngeal nodules were immunohistochemically stained as negative controls. Samples from 74% of 27 patients with laryngeal carcinomas demonstrated positive nuclear and cytoplasmic (or membranous) staining for p53 protein and 48% were positive for c-erbB-2 protein. In the present study, while there was a slight difference in the frequency of p53 over-expression among stage I-II and stage III-IV tumors, there was no difference in the frequency of p53 over-expression among primary and recurrent tumors. There was no statistically significant correlation between over-expression of the p53 and c-erbB-2 proteins and the age of the patients, tumor site, tumor grade, clinical stage, histopathological grading of the tumor, alcohol consumption, and clinical outcome. There was a statistically significant correlation between immunostaining of p53 and c-erbB-2 proteins (P = 0.037). While it was found that over-expression of p53 was significantly associated with the presence of lymph node metastasis (P = 0.006), there was no association between the expression of c-erbB-2 and lymph node status. The data demonstrated increased expression of p53 and c-erbB-2 proteins, presumed to be mutant, in laryngeal carcinomas. Hence, we conclude that p53 and c-erbB-2 over-expression as detected by immunohistochemical staining in larynx carcinomas is not predictive of poor survival or disease-free survival.

Clinicopathologic and familial characteristics of endometrial carcinoma with multiple primary carcinomas in relation to the loss of protein expression of MSH2 and MLH1.

The frequency of synchronous or metachronous multiple primary carcinomas in patients with endometrial carcinoma has been reported to be between 10% and 23% and is highest among all gynecologic carcinomas. However, clinical characteristics and underlying genetic abnormalities in endometrial carcinoma with multiple primary carcinomas has not been well clarified. Endometrial carcinoma is the most commonly associated extracolonic malignancy in hereditary nonpolyposis colorectal carcinoma in which germ line mutations in DNA mismatch repair genes, particularly in MSH2 and MLH1, are known to cause this syndrome. The purpose of the current study was to investigate clinicopathologic and familial characteristics including MSH2, MLH1, and p53 expression in endometrial carcinoma with multiple primary carcinomas, by comparing them to endometrial carcinoma without other primary malignancies. Patients were divided into two groups: 30 patients with synchronous or metachronous multiple primary carcinomas other than endometrial carcinoma and 116 patients with endometrial carcinoma without other primary malignancies. Clinicopathologic characteristics, family history of cancer, and immunohistochemical protein expression of MSH2, MLH1, and p53 expression were investigated in both groups, and 15 endometria from benign disease were used for normal controls in immunohistochemistry. The frequency of high risk clinicopathologic factors of endometrial carcinoma and 5-year survival rates and the frequency of p53 overexpression were not statistically different between the two groups. However, the loss of MSH2 and/or MLH1 expression was significant in endometrial carcinoma with multiple primary carcinomas, when compared with endometrial carcinoma alone (22 of 30 vs. 31 of 116). In cases with multiple primary carcinomas, particularly those diagnosed before the patient was 55 years of age or those in which the patient had a family history of cancer, the frequency of this loss was especially high (11 of 13 and 10 of 11, respectively). The clinical or biologic nature of endometrial carcinoma with multiple primary carcinomas seems to be similar to endometrial carcinoma alone. A high incidence of defective MSH2 and MLH1 protein in endometrial carcinoma with multiple primary carcinomas, however, suggests that abnormalities in the function of MSH2 and MLH1 may play an important role in tumorigenesis for patients with endometrial carcinoma with multiple primary carcinomas and their families.

The biological and clinicopathological characteristics of right-sided colon cancer.

The biological characteristics of right-sided colon cancer were examined in 74 colon cancers with regard to clinicopathological parameters, proliferative activity and p53 expression. Significant differences between right-sided and left-sided colon cancer were found in age, tumor size, histological type and lymphatic vessel invasion. The proliferating cell nuclear antigen labeling index did not significantly differ between the two cancers. The frequency of p53 overexpression was lower in the former than in the latter. The results suggested that right-sided colon cancer did not differ from left-sided colon cancer in proliferative activity except for its tendency to be locally advanced and to differ in carcinogenesis.

P53 nuclear accumulation in preneoplastic lesions and stage I uterine endometrioid adenocarcinoma

A total of 118 endometrial neoplastic and preneoplastic lesions comprising 43 uterine endometrioid adenocarcinoma at stage I, 40 complex (adenomatous) hyperplasias and 35 atypical hyperplasias were examined for p53 nuclear accumulation to assess the incidence of p53 alterations in infiltrating carcinomas and to verify if p53 aberrations may allow the identification of a subset of premalignant cases with high risk of progression. No specific immunostaining was observed in the cases of complex hyperplasia without atypias. One (3%) of 35 atypical hyperplasias showed focal areas of p53 immuno-reactivity. The overall frequency of p53 overexpression in endometrial carcinomas was 54%. The distribution of cases with nuclear accumulation of p53 was significantly different (p=0.01) in tumours with different degree of invasiveness. In addition, p53 nuclear accumulation was observed more often in tumours with moderate (G2) or poor differentiation (G3) (p=0.03). Our data indicate that p53 aberrations are not early events in endometrial carcinogenesis and may be related with tumour progression and aggressiveness.

P53 overexpression in squamous cell carcinoma of the esophagus.

Coastal South Carolina has a high incidence of squamous cell carcinoma of the esophagus (SCCE) among black residents. Overexpression and mutations of the p53 tumor suppressor gene have been noted in SCCE from other high-incidence regions. The purpose of this study was to determine the frequency of p53 overexpression in this region both in patients with SCCE and in normal subjects. Normal and malignant tissue obtained at esophagoscopy and normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal antibodies to the p53 gene product. Total cellular RNA was extracted from SCCE, reverse transcribed to complementary DNA, and a portion of the p53 gene was amplified via polymerase chain reaction and sequenced. Immunohistochemical studies on SCCE from nine patients showed that six (67%) were positive, two (22%) were negative, and one was indeterminate for p53 overexpression. The corresponding normal samples showed that three (33%) had p53-positive cells in the basal epithelial layer, whereas six did not. NEM from 18 random forensic cases displayed p53 overexpression in seven (39%). Eight of the nine tumors had p53 mutations. p53 overexpression and mutations are frequently found in SCCE from patients in coastal South Carolina. Overexpression in normal epithelium from random autopsy cases may indicate an inherited or acquired predisposition in this geographic region.

Clinico-pathological features and p53 expression in left-sided sporadic colorectal cancers with and without microsatellite instability.

Defects in mismatch repair (MMR) can result in the development of a 'mutator phenotype', manifest as an increase in DNA replication errors (RERs). Patients with hereditary non-polyposis colorectal cancer (HNPCC) have germline mutations in MMR genes. These patients develop carcinomas of the colon and other specific sites at a significantly earlier age than patients with sporadic carcinomas. RERs are found in the cancers from patients with HNPCC and have been demonstrated in 10-20 per cent of sporadic colorectal cancers (CRCs). Loss of MMR may simply accelerate tumour development, but it is also possible that these tumours follow a different carcinogenetic pathway from tumours with intact MMR. In particular, it has been suggested that p53 mutations occur less often in RER-positive (RER+) sporadic colorectal cancers. In this study, the clinico-pathological features and frequency of p53 overexpression in 17 left-sided RER+ CRCs were compared with 35 left-sided RER- CRCs. No differences were found in the age and tumour stage at presentation, mucinous differentiation, or Jass prognostic grouping between these two types of CRC. Thirteen out of 17 (76 per cent) RER+ and 19/35 (54 per cent) RER- tumours showed overexpression of p53, a non-significant difference (chi 2 test). Although some previous studies have suggested differences in the clinico-pathological features and p53 expression of RER+ and RER- right-sided CRCs, our results show that these differences do not exist in left-sided cancers.

Low frequency of p53 gene mutation and protein expression in mucinous colorectal carcinomas.

Immunohistochemical data indicate that the frequency of p53 protein overexpression is consistently lower in the mucinous than in the non-mucinous carcinomas of the breast, ovary, pancreas and colon. This peculiar immunohistochemical behavior of the mucinous phenotype could be due to the effect of large amounts of mucus on the staining or to an actual mutation frequency difference between mucinous and non-mucinous carcinomas. This question was investigated on a group of mucinous colorectal carcinomas. DNA was extracted from paraffin sections of 16 human mucinous colorectal carcinomas and the mutation frequency was determined by sequencing of p53 exons amplified in PCR. The expression of p53 protein was determined with the avidin-biotin complex-peroxidase staining procedure and CM-1 antiserum. Twenty-five percent of the tumors, exhibited p53 protein overexpression and in 31% a mutation was detected. Concordance between the two techniques was found in 69% of tumors. Overexpression without mutation was observed in 12% and mutation without overexpression in 19%. G:C --> A:T transitions represented the most frequent lesion (80%), as previously observed in non-mucinous colorectal carcinomas. These data indicate that the mutation pattern in the p53 gene is similar in mucinous and non-mucinous colorectal carcinomas. The low frequency of p53 overexpression in the mucinous phenotype is not due to a mucus effect on the staining but is related to the low mutation frequency of p53 gene. These results lead to the hypothesis that in contrast to the nonmucinous tumors the development of the majority of colonic carcinomas with the mucinous phenotype may be independent from p53 mutations.

736 P53 protein expression in colorectal cancer

P53 protein expression was examined in 204 surgically removed colorectal adenocarcinomas by immunohistochemistry using frozen tissue sections and monoclonal antibody DO7. Nuclear staining of more than 5% of neoplastic cells was observed in 124 (60.8%) tumours, which were classified as p53 positive. p53 immunoreactivity was found to be unrelated to several clinical and pathological variables, including age and sex of patients, tumour site, tumour stage and grade of differentiation. p53 expression was demonstrated to be closely related to the flow cytometric nuclear DNA content of the tumour. DNA diploid carcinomas and aneuploid tumours with DNA index (DI) ≤ 1. 20 had similar frequencies of p53 positive staining (40.9% and 48.1%, respectively), whereas aneuploid carcinomas with D > 1.20 had a significantly higher frequency of p53 overexpression (69.6%) (P = 0.0003). With respect to the total study population (mean follow-up 20.6 months; range, 9‐35 months) the duration of overall survival was independent of p53 expression. However, in the group of 141 patients with TNM stage I‐II‐III disease who had undergone curative resection, positive p53 staining was associated with poorer disease-free (P = 0.076) and overall survival (P = 0.025). Our results provide supporting evidence that p53 expression may represent an independent prognostic parameter in colorectal cancer.

P53 mutation in metastatic melanomas and primary melanomas from sun‐exposed and sun‐protected sites

AbstractBackground p53 mutation has been observed in many human malignancies, including skin cancers. However, the data in melanoma has been conflicting.Material and methods We have examined, by immunohistochemistry, using the DO7 and CM1 antibodies, the frequency of p53 overexpression in 14 metastatic melanomas and 61 primary melanomas, of which 30 were from sun‐protected sites and 31 from sun‐exposed sites.Results Ten of 14 metastatic melanomas showed p53 overexpression compared to only eight of 61 primary melanomas (P &lt; 0.004). No significant difference in p53 expression was found between primary melanomas from sun‐protected (2/30) and sun‐exposed sites (6/31). We have also examined p53 mutation by single‐strand conformation polymorphism (SSCP) analysis of four melanoma cell lines. One cell line established from a primary melanoma from a sun‐protected site showed evidence of an altered migration pattern in exon 7. Sequencing analysis of this region confirmed a point mutation in codon 244, showing a G to C transversion. This mutation is unlikely to be due to ultraviolet (UV) radiation since mutations caused by UV radiation are predominantly CC → TT or C → T transitions.Conclusions In summary, p53 mutation in primary melanoma is uncommon and does not appear to be related to UV radiation. p53 mutation is more common in metastatic melanomas suggesting that it may be involved as a late event in melanoma progression.

P53 mutation in metastatic melanomas and primary melanomas from sun-exposed and sun-protected sites

Background p53 mutation has been observed in many human malignancies, including skin cancers. However, the data in melanoma has been conflicting.Material and methods We have examined, by immunohistochemistry, using the DO7 and CM1 antibodies, the frequency of p53 overexpression in 14 metastatic melanomas and 61 primary melanomas, of which 30 were from sun-protected sites and 31 from sun-exposed sites.Results Ten of 14 metastatic melanomas showed p53 overexpression compared to only eight of 61 primary melanomas (P < 0.004). No significant difference in p53 expression was found between primary melanomas from sun-protected (230) and sun-exposed sites (631). We have also examined p53 mutation by single-strand conformation polymorphism (SSCP) analysis of four melanoma cell lines. One cell line established from a primary melanoma from a sun-protected site showed evidence of an altered migration pattern in exon 7. Sequencing analysis of this region confirmed a point mutation in codon 244, showing a G to C transversion. This mutation is unlikely to be due to ultraviolet (UV) radiation since mutations caused by UV radiation are predominantly CC → TT or C → T transitions.Conclusions In summary, p53 mutation in primary melanoma is uncommon and does not appear to be related to UV radiation. p53 mutation is more common in metastatic melanomas suggesting that it may be involved as a late event in melanoma progression.

Mutation and expression of TP53 in malignant melanomas.

Mutations of the TP53 gene are the most common genetic alterations in human malignancies. Overexpression of the p53 protein has been reported in high frequencies in all types of skin cancer. To determine the role of TP53 in the pathogenesis of malignant melanoma, we investigated the expression of p53 in 12 cell lines and 145 primary and metastatic lesions by immunohistochemistry. Overexpression of p53 was predominantly detected in the cytoplasm of the cells in 96 (66%) tumor and 12 (93%) cell lines. In contrast to findings in other tumor types, in melanomas immunoreactive cells were found in clusters or as scattered single cells. In primary melanomas, the frequency of p53 overexpression did not correlate with tumor thickness. Nucleotide sequencing of TP53 genes of 24 melanoma tumors/cell lines demonstrated point mutations in seven samples, all coding for mutant p53 protein species. The frequency of TP53 alterations of 20%-30% is lower than in other skin tumor types. Notably, immunohistochemistry was not a suitable method to distinguish overexpression of wild-type p53 from mutant species, since cell lines/tumors with TP53 mutations did not show distinctive staining patterns. The mutation pattern in six out of seven lesions was similar to that caused by ultraviolet light damage. This finding may be regarded a further indication for a pathogenetic role of UV light damage in at least a subgroup of malignant melanomas.

P53 expression and K-ras mutation in colorectal adenomas.

The frequency of p53 overexpression and K-ras codon 12 mutation was investigated in a series of colorectal adenomas. p53 was detected by immunohistochemistry in only 5% of tumours, whereas K-ras mutation was found in eight of 30 adenomas examined. In vitro, mutant p53 and ras genes cooperate to transform primary rat cells into a tumourigenic cell line. The presence of both p53 overexpression and K-ras mutation in a benign tubulovillous polyp in the present series suggests that in vivo this combination of events is insufficient to cause malignant transformation of a large bowel adenoma.