Urological Oncology Relationship Between Expression of p53 Protein and Tumor Subtype and Grade in Renal Cell Carcinoma
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Introduction: Our aim was to evaluate the overexpression of p53 protein, product of mutated TP53 gene, in histologic sections of the kidneys with renal cell carcinoma (RCC) and its association with tumor grade and subtype. Materials and Methods: A total of 66 histologic sections of the kidneys of patients with the diagnosis of RCC were re-evaluated and tumor grade, tumor subtype, and p53 expression were determined. Results: Of the total 66 histologic sections with the diagnosis of RCC, 34 (51.5%), 27 (41%), and 5 (7.5%) were conventional, papillary, and chromophobe subtypes, respectively. Fifty-one (77.3%), 14 (21.2%), and 1 (1.5%) of tumors were grade 2, 3, and 4, respectively. Thirty (45.4%) sections were positive for p53 immunohistochemical staining. In 7 cases (20.6%) of the conventional tumors, p53 staining was positive, while 18 papillary (66.6%) and 5 chromophobe tumors (100%) had a positive staining for p53 (P < .001). Seventeen out of 51 grade 2 tumors (33.4%) and 12 out of 14 grade 3 tumors (85.7%) were positive for p53. The single case of grade 4 tumor was positive for p53 protein, too (P = .001). Conclusion: Increased expression of p53 protein is rather prevalent in RCC. This factor is associated with tumor grade and subtype. According to our findings, it is generally accompanied by nonconventional subtypes and higher tumor grades.Keywords:
Chromophobe cell
P53 protein
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In the present study, immunohistochemical expression of HER 2 NEU, P53 & P63 were evaluated in urothelial carcinoma of the urinary bladder for a period of two years from June 2015- June 2017 in the Institute of Pathology, Madras Medical College & Rajiv Gandhi Government General Hospital, Chennai. The immunohistochemical expression of these markers were correlated with various clinico-pathological variables like age, gender, tumor size, grade, stage and invasiveness of the tumor. We also analyzed the correlation between HER 2 NEU with P53, HER 2 NEU with P63 and P53 expression with P63 expression. We performed both prospective and retrospective data analysis of patients who were diagnosed to have biopsy proven urothelial carcinoma and were included in the study population. The exclusion criteria included all benign & non neoplastic lesions of the bladder and other histological variants of urothelial carcinoma like micropapillary variant, urothelial carcinoma with squamoid differentiation, squamous cell carcinoma of bladder. We received 22,178 specimens for histopathological examination during the study period and 123 were bladder specimens. Out of 123 bladder specimens, 84 cases were diagnosed as urothelial carcinoma, 32 were reported as non neoplastic & benign lesions and conclusive opinion could not be arrived in 7 cases because of inadequate sampling. Among 84 cases, 46 (55%) were high grade and 38 (45%) were low grade urothelial carcinoma. We selected 52 cases of urothelial carcinoma from 84 cases and this constituted equal proportion of high (26 cases) grade and low (26 cases) grade urothelial carcinoma for easy comparison. Among 26 high grade urothelial carcinoma, 24 (92%) were muscle invasive and 2 (8%) were non muscle invasive carcinoma. Of 26 low grade urothelial carcinoma, 5 (19%) were muscle invasive and 21 (81%) were non muscle invasive.
In the present series, the peak incidence of urothelial carcinoma was above 50 years of age. Males constituted 69% and females accounted for 31% of cases. The lateral wall was the most common site of urothelial carcinoma followed by posterolateral wall. It was found that urine cytology showed higher sensitivity for high grade urothelial carcinoma than low grade urothelial carcinoma. Most high grade carcinoma were stage II & III, whereas most low grade were stage I & II carcinoma and a significant statistical correlation was observed between the grade and the stage of the tumor.
Immunohistochemical expression of HER 2 NEU showed significant statistical correlation with tumor grade and no correlation was observed with age, gender, size, stage and invasiveness of the tumor. P53 over expression correlated with tumor grade, stage and invasiveness of the tumor and no correlation was observed with age, gender and size of the tumor. There exists a statistical correlation between decreased expression of P63 and grade, invasiveness, size, stage and no correlation was observed with age, sex. HER 2 NEU expression showed correlation with P53 over expression and decreased P63 expression. A significant statistical correlation was observed between P53 over expression and decreased expression of P63.
It is inferred that HER 2 NEU over expressing patients would be benefited from targeted therapy and it could be considered as prognostic marker in the future. Similarly, over expression of P53 and decreased expression of P63 could be considered as surrogate molecular markers affecting the prognosis and outcome of the patient. Thus these markers aids in risk stratification and management of the patient.
Carcinoma in situ
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Background. Investigation of p53 immunoreactivity in formalin-fixed paraffin-embedded tissues of normal renal tissue and renal cell carcinoma with respect to histopathologic subtype and nuclear grade of RCC. Methods. 42 tissue sections of RCC and 5 samples of normal renal tissue were stained for p53 expression using immunohistochemical assay. The results were analyzed in relation to nuclear grade and histopathologic subtype. Results. In total, p53 expression was found to be 4 to 5 times higher (30.8%) in other types of RCC than in the clearcell type of RCC (6.9%). Further, there was no statistically significant difference in p53 overexpression among the histopathologic subtypes (P>0.05, P=0.063). No association was found between the expression of p53 and nuclear grade (P>0.05, P=0.17). Interestingly, our study also showed weak cytoplasmic positivity in renal tubular epithelium. Conclusion. Our findings suggest that p53 might play an important role in tumour development or progression and it might be used as a new predictor and therapeutic target for RCC.
P53 protein
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The purpose of our study was to examine the frequency of p53 mutation and bcl-2 expression in transitional cell carcinoma of the urinary bladder and their clinicopathologic correlates.A total of 137 patients who underwent transurethral resection for primary transitional cell bladder carcinomas were enrolled. The paraffin-embedded tissue blocks were recut and stained by monoclonal anti-p53 (DO7) and anti-bcl-2 (124) antibodies. The bcl-2 and p53 immunoreactivity was correlated to tumor grade and pathological stage.p53 mutation was identified in 102 patients (78.5%). The mutation was most common in grade 3 tumors (95%) as compared to grade 2 (74%) and grade 1 (80%) tumors, but the difference was not statistically significant (p = 0.289). Stage pT2 tumors had higher incidence of p53 mutation (97%) as compared to pTa-1 tumors (71%, p = 0.0003). Only 17 tumors (13%) expressed bcl-2; the grade 3 tumors had significantly higher incidence of bcl-2 expression (p = 0.04). The bcl-2 expression was not related to pathological stage (p = 0.083). There was no interrelation between p53 mutation and bcl-2 expression (p = 0.97). Grade 3 tumors correlated well with invasive disease (p < 0.00001). When grade 2 tumors were evaluated separately, p53 mutation was positively correlated with disease invasion (p = 0.001).Grade 3 tumor was the most important variable associated with tumor invasion in transitional cell carcinoma of the urinary bladder. p53 mutation was positively correlated with invasive disease. Grade 2 tumors with p53 mutation had greater probability of disease invasion. Expression of bcl-2 positively correlated with tumor grade but not pathological stage.
Bladder Neoplasm
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Ovarian cancers remain the most lethal of all gynecological malignancies despite major developments in their treatment.To study the rate of expression and staining patterns of p53 in various histological types and grades of epithelial ovarian tumors (EOT).Sixty EOTs received in a tertiary care center were studied for gross, microscopy, and p53 immunohistochemistry (IHC) expression patterns. Parameters such as age, laterality of tumor, ascites, capsule rupture, tumor size, stage at presentation, metastasis, tumor grade, and number of mitosis were correlated.Of the sixty cases studied, 23 (38.3%) were malignant. Serous carcinomas were the largest group with 17 cases (74%) followed by mucinous with 4 cases (17%) and 2 clear cell carcinomas (9%). All benign and borderline EOT were p53 negative. 65.2% of the malignancies were p53 positive and all of them were serous malignancies. 15 out of 16 high-grade serous carcinomas were p53 positive (94%), while one case was negative (6%). 10 cases (63%) showed intense diffuse positivity of more than 60% of the nucleus, while 5 cases (31%) showed aberrant null staining <5% staining of the nucleus. All mucinous, clear cell carcinomas, and the only low-grade serous carcinoma in the study were p53 negative. P53 staining had positive correlations with variables like capsule rupture, ascites, laterality, and CA 125.The study highlights the different rates of expression and staining patterns of p53 and the need for correct interpretation of p53 IHC for the diagnosis of various EOT.
Clear cell carcinoma
Serous carcinoma
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The aim of this study was to investigate the relationship of AEG-1 and p53 with the prognostic parameters of renal cell carcinoma (RCC). In this study, 50 paraffin blocks were histopathologically diagnosed at the Department of Pathology of the Medical Hospital of Duzce University, between 2005 and 2011. The cases consisted of 24 clear cell (CC) and 26 non-clear cell (NCC) RCC subtypes as follows: 24 (48%) clear cell RCC, 12 (24%) papillary RCC, 4 (8%) multilocular cystic RCC and 10 (20%) chromophobe RCC; none had sarcomatoid changes. By immunohistochemical analysis we investigated AEG-1 and p53 expression in carcinomas of the kidney, and by statistical analysis determined their relationship with clinicopathological parameters. Significant relationships were found between increasing tumor diameter and the increase of p53 (p = 0.028). In addition, p53 was significantly related to renal sinus invasion (p = 0.05) and Fuhrman grade (p = 0.026). There was a significant relationship between increased AEG-1 staining scores and CC and NCC carcinoma subtypes (p = 0.032), tumor capsule invasion (p = 0.01) and lymphovascular invasion (p = 0.015). There was also a significant correlation between tumor size and capsule and lymphovascular invasion (p = 0.02). We concluded that high AEG-1 and p53 expression correlates with the prognostic parameters in RCC patients, and in addition may be associated with tumor progression.
Chromophobe cell
Lymphovascular invasion
Tissue microarray
Renal sinus
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To investigate the immunohistochemical expressions of p53, ki67, CK20 in superficial papillary urothelial neoplasms of the bladder and correlate them with histological grade, tumor progression and recurrence.We selected samples of 43 patients with superficial transitional cell carcinoma of the bladder. They were divided into two groups, one called Recurrent (R), with 18 individuals, and other Non-Recurrent (NR), with 25. Multi-sampling blocks were prepared. The immunohistochemical technique employed was immunoperoxidase, and the antibodies were: p53: Novocastra (clone DO7) at a dilution of 1/100; Ki67: Spring (clone SP6) at a dilution of 1/100; and CK20: Dako (clone K20 .8) at a dilution of 1/50.The expression of p53 was observed in 11 cases, six in the Recurrent group and five in the Non-Recurrent, all high-grade tumors (p = 0.0001). The histological progression occurred in six patients (p = 0.0076). Of the 18 Recurrent cases, six showed immunoreactivity for p53 and 12 were negative for this antibody (p = 0.1715). Ki67 was positive in 17 of the 18 cases from the Recurrent group (p = 0.0001) and, from 20 high-grade tumors, 18 showed reaction to this antibody (p = 0.0001). Of the 18 individuals who had recurrence, 13 showed anomalous expression for CK20 (p = 0.0166). In high-grade carcinomas, of the 20 cases, 16 showed anomalous expression for this antibody, while 18 of the 23 patients with low-grade tumors showed normal expression for CK20 (p = 0.0002).The p53 showed good correlation with histological progression and histologic grade. Ki67 was strongly associated with recurrence and histological grade, and CK20 was also associated with these variables.
Immunoperoxidase
clone (Java method)
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P53 gene mutation has been described with variable frequency in gastric cancer and its biological significance remains unclear. We studied 101 gastric carcinomas to evaluate the association between this genetic alteration and the evolution of gastric cancer. Of these, 67 patients were men and 34 were women. The median age at diagnosis was 68 years. The tumors were obtained from gastrectomies. The p53 gene mutation was determined with the monoclonal antibody DO7 (Novocastra). The neoplasms were classified as tumors with high or low level p53 expression according to the intensity and distribution of the nuclear staining. Forty eight tumors showed high level of p53 immunoreactivity. The association of p53 expression with age, sex, tumor size, histologic type, histologic grade, depth of invasion, localization, lymph node metastases, type of surgery and 5 year survival rate was investigated. The results did not demonstrate any significant association between p53 expression and the factors mentioned above.
P53 protein
P53 expression
Gastric carcinoma
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OBJECTIVE To determine the ability of p63 reactivity to confirm the diagnosis of urothelial carcinomas (UCs) that present clinically as kidney masses and to determine the association of p63 expression with clinicopathologic features in UCs. STUDY DESIGN The study included 27 patients with renal pelvis UC and 42 patients with renal cell carcinoma (RCC). p63 Reactivity was examined immunohistochemically in tumor and nonneoplastic tissues. Correlation of p63 expression in renal malignancies (RCCs and UCs) was investigated and compared with clinicopathologic parameters. RESULTS p63 Expression was detected in 25 of 27 (92.6%) UC cases while none of the RCC cases were positive for p63. There was a correlation between p63 expression and tumor stage, grade and survival time (p < 0.0001, = 0.032, = 0.028, respectively). However, no correlation was found between p63 expression and tumor progression (p = 0.513). CONCLUSION p63 Should be considered as an additional biomarker to distinguish UC from RCC. Decreased p63 immunoreactivity was significantly associated with advanced tumor stage and grade. p63 Reactivity appears to be a useful prognostic factor in UC.
Renal pelvis
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Our aim was to evaluate the overexpression of p53 protein, product of mutated TP53 gene, in histologic sections of the kidneys with renal cell carcinoma (RCC) and its association with tumor grade and subtype.A total of 66 histologic sections of the kidneys of patients with the diagnosis of RCC were re-evaluated and tumor grade, tumor subtype, and p53 expression were determined.Of the total 66 histologic sections with the diagnosis of RCC, 34 (51.5%), 27 (41%), and 5 (7.5%) were conventional, papillary, and chromophobe subtypes, respectively. Fifty-one (77.3%), 14 (21.2%), and 1 (1.5%) of tumors were grade 2, 3, and 4, respectively. Thirty (45.4%) sections were positive for p53 immunohistochemical staining. In 7 cases (20.6%) of the conventional tumors, p53 staining was positive, while 18 papillary (66.6%) and 5 chromophobe tumors (100%) had a positive staining for p53 (P < .001). Seventeen out of 51 grade 2 tumors (33.4%) and 12 out of 14 grade 3 tumors (85.7%) were positive for p53. The single case of grade 4 tumor was positive for p53 protein, too (P = .001).Increased expression of p53 protein is rather prevalent in RCC. This factor is associated with tumor grade and subtype. According to our findings, it is generally accompanied by nonconventional subtypes and higher tumor grades.
Chromophobe cell
P53 protein
Positive staining
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Background: Urothelial cancer (UCa) poses a significant medical and public health concern in most parts of the world and is defined as a pan- urothelial disease in which entire urothelium of the renal pelvis to the urethra can undergo malignant transformation. Bladder tumors account for 90–95% of urothelial carcinomas and are the most common urinary tract malignancy. It is three times less common in females.
Methods: The study was conducted on 40 cases of Urothelial Carcinoma received as biopsy specimens in a tertiary care hospital. There were 20 cases each of low grade and high grade and after grading these were subjected to p63 expression.
Result: 78% of the patients were from 50-75 year age group with Male to Female ratio being 4:1. Painless hematuria was most common complaint. The size varied from 0.5 to 7.2 cm.
For P63, 38 (95%) cases showed positive p63 expression. Of which 20 cases were low grade and 18 (90%) were high grade papillary urothelial carcinomas. Of P63 positive cases 36 cases showed moderate to strong staining intensity whereas two cases showed mild staining intensity. The p63 expression decreased with grade and invasion.
Conclusion: P63 immunoexpression decreases with increasing grade of tumor as well as with invasion thus showing that its expression is related with good prognosis.
Renal pelvis
Grading (engineering)
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