Co-expression of p53 by epithelial and stromal elements in carcinosarcoma of the female genital tract: an immunohistochemical study of 19 cases

Carcinosarcoma is an aggressive neoplasm of the female genital tract, which comprises 1–2% of malignancies of the uterine corpus. Because of the broad range of differentiation exhibited by these tumors, the precise nature of the relationship between epithelial and stromal components in this unique tumor remain unclear. Previous studies have demonstrated that mutation and consequent overexpression of the tumor suppressor gene p53 occurs frequently in carcinosarcoma and is conserved from primary to metastastic sites. We examined p53 accumulation in formalin-fixed, paraffin-embedded archival sections in 19 cases previously shown to have mutations in the p53 gene and performed semi-quantitative analysis of the intensity of staining and relative density of positive cells and stromal and glandular elements. There was a high level of concordance of immunohistochemical staining for the p53 oncoprotein between glandular and stromal elements. These results further suggest a clonal origin for the diverse elements of carcinosarcoma.     

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.     

Bax,Bcl-2, and p53 expression in endometrial cancer

BACKGROUND: It has not been fully clarified whether alteration of Bax and other apoptosis-relating proteins of Bcl-2 and p53 is involved in endometrial carcinogenesis. METHODS: A total of 56 frozen tissues, which included 14 normal endometria, 13 endometrial hyperplasias (10 without atypia and 3 with atypia), and 29 endometrial carcinomas, were examined for the expression of Bax, Bcl-2, and p53 using immunohistochemistry. For Bax-negative cases, PCR-direct sequencing was performed for the bax gene. For cases with p53 overexpression, mutational analysis was performed for the p53 gene using a yeast functional assay and sequencing. RESULTS: Both Bax and Bcl-2 were distinctly expressed in the normal proliferative phase endometrium. A decreased Bcl-2/Bax ratio in the secretory phase endometrial gland cells due to suppressed Bcl-2 expression was observed. Bax expression was positive in all 13 endometrial hyperplasias, while it was absent in 6 of 29 endometrial carcinomas (20.7%). Negative Bax expression in endometrial carcinoma was not related to tumor stage, histologic subtype, or other histopathologic prognostic factors. Bax expression showed no relationship to either p53 overexpression or Bcl-2 expression. In the DNA of 6 Bax-negative cases, we found a frameshift insertion mutation at codon 58 (AAG to CAAG) in the BH3 domain despite the absence of mutation in the (G)8 tract, suggesting that this codon may be another preferred target for bax mutation other than the (G)8 tract. Mutational analysis was available for 7 of 10 cases with p53 overexpression, in which 5 cases were found to have a missense mutation and 2 cases had no mutation of the p53 gene. At least 10 of 29 (34.5%) cases of endometrial carcinoma were associated with sequence-verified mutation in the bax gene and/or p53 gene. CONCLUSIONS: The bax gene frameshift mutation appears to cause a loss of Bax expression in endometrial carcinoma. Codon 58 may be a preferred target of bax gene mutation in endometrial carcinomas. The bax gene mutation seems to occur in the early stage of the genesis of a subset of endometrial carcinomas.     

p27 and cyclin D1 abnormalities in uterine papillary serous carcinoma

OBJECTIVE: The expression status of p27 and cyclin D1 was examined in 21 uterine papillary serous carcinoma (UPSC) specimens to determine the role of these genes in the development of this disease. The status of p53, p16, Rb, and K-ras was also determined in these tissues so that a marker profile for UPSC could be compared with the published marker profile for other forms of endometrial and ovarian cancer. METHODS: Immunohistochemistry was performed on 21 UPSC tissue sections to determine the expression status of p27, cyclin D1, p53, p16, and Rb. K-ras mutations were identified by restriction fragment length polymorphism analysis of DNA isolated from the UPSC sections. RESULTS: All specimens displayed at least one molecular abnormality. A high incidence of p27 alterations were observed, with reduced p27 expression measured in 16 of 21 (76%) tumors, followed by p53 alterations observed in 13 of 21 (62%) tumors. The p27 abnormalities occur at an early stage of the disease, with 63% (5/8) of Stage I cases displaying reduced p27 expression. Cyclin D1 overexpression was observed in 4 of 21 (19%) specimens, whereas p16, Rb, and K-ras abnormalities were each observed in 2 of 21 specimens (10%). Both K-ras mutations were at codon 12. The p16 and Rb abnormalities coexisted in the same specimens. CONCLUSION: UPSC tumors display a high incidence of p27 abnormalities, suggesting that p27 abnormalities play an important role in the development of this disease. Our results also indicate that cyclin D1 overexpression is involved in the development of a small number of UPSC cases. A comparison of our results with reports by other authors suggests that UPSC shares molecular marker alterations with both ovarian cancer and endometrioid adenocarcinoma.     

Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium

We aimed to investigate if expressions of survivin and p27 proteins are involved in the development of endometrioid carcinoma, along with whether there are any correlations between these proteins and loss of wild-type PTEN that is found in up to 80% of endometrial carcinomas. We also studied their correlations with classical prognostic factors and survival in endometrial carcinoma. To our knowledge, this is the first time survivin expression is investigated in endometrial hyperplasia along with endometrioid adenocarcinoma. For immunohistochemical analysis, 29 endometrioid adenocarcinoma, 38 endometrial hyperplasia, and 10 proliferative endometrium tissue samples were selected in the pathology archives. Staining of cells was scored as +2 if >50%, +1 if <50%, and negative if none were stained positive. Survivin expression increased from proliferative to hyperplasia to carcinoma cases. PTEN and p27 expressions decreased in hyperplasia and carcinoma cases with respect to proliferative endometrium. All these differences were statistically significant (P < 0.05). PTEN positively correlated to p27 (P < 0.05); however, neither was correlated with survivin. None of these genes were correlated with classical prognostic factors such as grade and myometrial invasion in endometrioid adenocarcinoma. However, mean survival was statistically significantly higher in PTEN-positive cases (46.6 vs 16.4 months) (P < 0.05). Survivin overexpression might be one of the important mechanisms in the development of endometrioid adenocarcinoma along with lost or decreased activity of PTEN and p27. However, survivin seems to exert its role in ways different from those of PTEN or p27 in the development of endometrioid adenocarcinoma. These findings on the role of survivin in endometrioid adenocarcinoma should be confirmed and the pathways through which survivin acts in endometrioid adenocarcinoma studied further with a larger sample size.     

子宫内膜癌p53蛋白过度表达与性激素受体阳性的关系

目的：研究子宫内膜癌ｐ５３蛋白过度表达与性激素受体阳性的关系。方法：收集４５例子宫内膜癌手术标本，采用多种ＰＡＰ免疫组化方法进行检测。结果：４５例宫内膜癌中１４例（３１．１％）ｐ５３蛋白过度表达，其中１１例雌、孕激素受体阴性，而在ｐ５３阴性的３１例中２７例雌、孕激素受体阳性。在子宫内膜癌中ｐ５３蛋白过度表达与雌、孕激素受体呈负相关（Ｐ＜０．０１）。结论：部分子宫内膜癌的发生可能与雌激素受体无关，而与ｐ５３蛋白过度表达有关。     

Assessment of inhibin and p53 in granulosa cell tumors of the ovary

OBJECTIVE: The goal of this work was to determine the cellular content of inhibin and p53 in granulosa cell tumors (GCTs). METHODS: Clinical records of 47 patients (mean age, 54 years; range, 20-85 years) presenting with GCT surgically managed at our institution were abstracted. International Federation of Gynecology stage I was assigned in 39 patients, stage II in 2, and stage III in 6. Concomitant endometrial carcinoma was identified in 6 patients. Mean follow-up was 13.6 years (range, 1 day to 37.6 years). Sections from paraffin-embedded tissue blocks were analyzed immunohistochemically for expression of tissue inhibin and p53 levels. Inhibin expression was graded by intensity and reactivity, and p53, by its presence or absence. RESULTS: The tumors of 27 patients (57%) stained strongly for inhibin intensity and showed >60% reactivity. Decreased intensity and reactivity of inhibin expression were associated with advanced-stage disease (P = 0.05 and P < 0.01, respectively, by Fisher exact test). Expression of p53 was detected in tumors from 27 patients (57%), and immunoreactivity was associated with compromised progression-free survival (P = 0.016, log-rank test). However, the association between p53 immunoreactivity and disease stage was not significant. Absence of p53 expression was significantly associated with concurrent endometrial carcinoma (P = 0.022), suggesting more molecularly intact tumors that retain functional activity. CONCLUSIONS: Although the majority of GCTs show strong expression of inhibin with regard to intensity and reactivity, weak expression is associated with advanced disease but not with decreased progression-free survival. By contrast, expression of p53 is not significantly associated with stage, but increased expression is associated with decreased disease-free survival. Absence of p53 expression appears to be associated with concurrent endometrial carcinoma.     

Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma

Abstract.   Watanabe J, Watanabe K, Jobo T, Kamata Y, Kawaguchi M, Imai M, Okayasu I, Kuramoto H. Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 452–457.
We reported that p27 induced by medroxyprogesterone acetate (MPA) may be involved in the progestin-induced growth suppression of human endometrial adenocarcinoma cells. This study aimed at investigating whether p27 expression could be a predicting marker to evaluate the effectiveness of MPA therapy. The clinical responses of 15 patients with endometrial carcinoma treated with MPA were examined. p27 expression was evaluated by immunohistochemical staining. Percentage of positive nuclear staining was expressed as a strongly positive (SP) labeling index (LI). Before MPA treatment, SP LIs in the effective and noneffective groups were 22.6 ± 14.3% and 9.1 ± 9.2%. At 1–6 weeks in the MPA treatment, SP LIs increased in both groups and were significantly higher than those before the therapy. At 7–12 weeks, SP LIs in both groups decreased to the level of pretherapy. At 13–18 weeks, SP LIs in the effective group were 14.9 ± 5.7%, whereas in the noneffective group, 1.1 ± 2.0%. The former was significantly higher than the latter. p27 expression could predict the effectiveness of MPA treatment for endometrial carcinoma at an early stage of the 4-month period in MPA therapy and could be a useful predicting marker for MPA.     

p27kip1及p53基因蛋白与恶性卵巢上皮性肿瘤预后的关系

目的　探讨 p2 7kip1和 p5 3基因蛋白在恶性卵巢上皮性肿瘤中的表达及其与预后的关系。 方法　1992年 11月至 1999年 12月应用免疫组化检测 5 6例恶性卵巢上皮性肿瘤石蜡切片中 p2 7kip1和p5 3基因蛋白表达情况 ,并应用Kaplan -Mier法及多变量Cox比例风险回归模型分析患者预后。 结果　 5 6例恶性卵巢上皮性肿瘤患者的 p2 7kip1基因蛋白表达率为 4 1 1% ;p5 3基因蛋白表达率为 4 8 2 % ,两种基因蛋白表达比较 ,差异无显著性 (P >0 0 5 )。p2 7kip1及 p5 3基因蛋白表达与肿瘤的病理分级有关 ( P <0 0 5 ) ,与其他临床病理特征无关。单因素分析 :p2 7kip1及 p5 3基因蛋白表达与患者的中位生存时间、生存曲线各时点生存率密切相关。 结论　p2 7kip1基因蛋白表达对恶性卵巢上皮性肿瘤的预后有显著影响 ,而 p5 3基因蛋白表达与预后关系不显著     

p53 Expression as a Prognostic Indicator of 5-Year Survival in Endometrial Cancer

BACKGROUND: One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. The purpose of this article was to build upon the authors' previous work with p53 and determine whether p53 was a prognostic indicator of 5-year survival. METHODS: One hundred thirty-seven consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. All patients were evaluable for 5-year survival. RESULTS: One hundred three patients had endometrioid adenocarcinoma; 6, adenosquamous carcinoma; 14, papillary serous carcinoma; 10, clear cell carcinoma; and 4, undifferentiated carcinoma. p53 expression ranged from 0.0 to 58.2% positive nuclear area with a mean of 11.5% (median 2.6%) for the cohort. For the patients with endometrioid carcinoma, the mean p53 expression was 7.1% while for the nonendometrioid tumors it was 24.6% (P<0.001). Fifty-nine of the 103 endometrioid tumors (57.3%) stained positive for p53 while 32 of the 34 nonendometrioid (94.1%) tumors stained positive (P<0.001). Increasing histologic grade correlated with an increasing p53 expression (P = 0.003). The percentage of tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.003). However, mean p53 expression did not differ between early (stage I) and advanced (stage II, III, and IV) cancers (P = 0.088). Utilizing 5-year survival as the endpoint for multivariate analysis, FIGO stage (P = 0.0028) and p53 expression (P<0.001) were the only independent prognostic indicators found. CONCLUSION: p53 expression is more commonly found in nonendometrioid than in endometrioid adenocarcinoma of the endometrium. It, along with FIGO stage, is an independent prognostic indicator of 5-year survival.     

子宫内膜癌p53抑癌基因蛋白表达及其与预后的关系

为研究抑癌基因ｐ５３与子宫内膜癌的关系，本研究用免疫组化ＡＢＣ法检测了２３例正常子宫内膜、４４例子宫内膜增殖症及１０３例子宫内膜癌组织中抑癌基因ｐ５３的表达情况。结果表明：突变型ｐ５３蛋白在于宫内膜癌组织中的阳性率为４７．６％，而在正常子宫内膜及各类型子官内膜增殖症中均为阴性。突变型ｐ５３的表达与子宫内膜癌的病理类型、组织分化、脉管浸润情况及ＤＮＡ异倍体等因素有关。ｐ５３表达阳性者的生存率明显低于无表达者，５年生存率分别为５９．９％及８３．４％。用Ｃｏｘ比例风险模型计算，结果表明ｐ５３表达阳性者的死亡危险度为阴性者的６．３４倍。突变型ｐ５３蛋白的出现与子宫内膜癌的恶性生物学行为有关。     

The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers – a study of the National Cancer Institute of Canada Clinical Trials Group

A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.     

FHIT expression in neoplastic, hyperplastic, and normal endometrium

Fragile histidine triad (FHIT), a candidate of tumor suppressor protein, expression was examined on paraffin-embedded specimens in proliferative, secretory, hyperplastic, and neoplastic human endometrium by immunohistochemistry. The results of FHIT immunoreactivity in endometrial carcinomas were compared with prognostic indicators as well as with p53 overexpression. Forty-four cases of endometrial carcinoma, 30 normal functional (15 proliferative, 15 secretory), and 24 hyperplastic endometrium (12 without atypia, 12 with atypia) specimens were studied using polyclonal FHIT antibody. The streptavidin-biotin-peroxidase detection system was used, and the intensity and the distribution of immunoreactivity were evaluated semiquantitatively. There were no significant differences in FHIT expression in the proliferative, secretory, hyperplastic, either with or without atypia, or carcinomatous endometria. No significant difference in FHIT expression of endometrial carcinomas was detected when prognostic parameters or p53 overexpression were considered. Loss or reduced FHIT expression was not found to predict disease-free or cumulative survivals. This study showed that loss or reduction in FHIT protein expression is present in normal functional and hyperplastic endometria as well as in neoplastic endometrium. FHIT protein seems not to be involved directly in endometrial carcinogenesis, but rather, it regulates cell proliferation both in physiologic and in pathologic conditions of endometrium.     

Prognostic significance of Bcl-2, p53 overexpression,and lymph node metastasis in surgically staged endometrial carcinoma

OBJECTIVE: The purpose of this study was to clarify whether Bcl-2 and p53 have prognostic significance that is independent of lymph node metastasis and other conventional histopathologic factors in endometrial carcinoma. STUDY DESIGN: Immunohistochemistry for Bcl-2 and p53 expression was performed on the frozen sections of 102 cases that were treated with surgery, including pelvic and para-aortic lymphadenectomy. Cox regression analysis was used to determine the prognostic significance. RESULTS: By univariate analysis, both loss of Bcl-2 expression and p53 overexpression were related to patient survival. Lymph node metastasis, p53 overexpression, and nuclear grade were found to be independent prognostic factors (determined by multivariate analysis). The estimated 5-year survival rate of patients with stage III/IV disease without p53 overexpression was 75.7%; the estimated 5-year survival rate for patients with p53 overexpression was only 40.4%. The difference was highly significant (P =.0053). CONCLUSION: Lymph node metastasis, p53 overexpression, and nuclear grade are independent prognostic factors for endometrial carcinoma. Bcl-2 may have little importance in the progression of endometrial carcinoma and is a less potent prognostic factor than is p53. A new treatment strategy is necessary for advanced stage endometrial carcinoma with p53 overexpression.     

p27蛋白在子宫内膜癌组织中的表达及其临床意义

目的 :探讨p2 7在子宫内膜癌组织中的表达及其临床意义。方法 :采用免疫组化S -P法测定 16份正常子宫内膜、18份子宫内膜不典型增生及 50份子宫内膜癌组织中的p2 7蛋白表达。结果 :p2 7蛋白在子宫内膜癌、子宫内膜不典型增生及正常子宫内膜中的表达率分别为 34%、6 6 .6 7%和 93.75% ,正常子宫内膜及不典型增生组均显著高于子宫内膜癌组 ,差异有显著性 (P <0 .0 5)。p2 7蛋白表达与子宫内膜癌组织学分级、肌层浸润程度及患者预后显著相关 (P <0 .0 5) ,但与临床分期无关。结论 :p2 7蛋白表达下降或缺失可能在子宫内膜癌的发生、发展中起重要作用 ,并可能提示患者的预后     

The association between p53 expression, stage and histological features in endometrial cancer

OBJECTIVE: Alterations of the p53 gene have been widely suggested to be relevant to the development of endometrial carcinoma. However, contradictory results have been reported when immunohistochemical determination of p53 expression has been correlated with stage and histological features of the tumours. STUDY DESIGN: Pathology findings were reviewed and p53 immunoperoxidase staining was performed in 240 cases of endometrial carcinoma. RESULTS: Uterine papillary serous adenocarcinomas showed significantly higher p53 overexpression than uterine endometrioid adenocarcinomas (100.0% versus 61.0%, p<0.005). p53 overexpression was significantly higher in the secretory variant (85.7%) than in the typical endometrioid carcinoma (60.0%) (p<0.05). p53 expression did not differ between early (stage I) and advanced (stage II-IV) carcinomas. Likewise, no difference was observed in p53 expression among different architectural grades. The incidence of metastasis to lymph nodes was similar in p53 positive (13.7%) and in p53 negative tumours (12.5%). CONCLUSION: In the present series, p53 immunostaining did not differ between cases with different FIGO stages or histologic characteristics of the tumours. No simple relationship exists between the immunohistochemical determination of p53 expression and the biological aggressiveness of endometrial carcinomas.     

p53 expression in tissue adjacent to endometrial carcinoma

OBJECTIVE: Since several investigations did not demonstrate the presence of altered p53 in endometrial hyperplasias, it has been concluded that these alterations constitute a relatively late event in endometrial carcinoma. The aim of the present study was to assess the presence of p53 in the tissue adjacent to endometrial carcinoma in attempt to elucidate the relationship between these tissues. METHODS: New slides were prepared from paraffin-embeded tissue blocks of 49 endometrial endometrioid carcinoma hysterectomy specimens so that in each case tumor tissue and adjacent uninvolved endometrium were represented. Immunohistochemical staining for p53 detection was then performed. RESULTS: In 43 of the 49 hysterectomy specimens evaluated, the tissue adjacent to the endometrial carcinoma was non hyperplastic and in six it was hyperplastic. Positive immunohistochemical staining was found in 22 (44.9%) of endometrial carcinomas and in eight (16.3%) of the adjacent tissues. A statistically significant higher percentage of hyperplastic adjacent tissues than non-hyperplastic adjacent tissues were immunohistochemically p53 positive (50.0% vs 11.3%; p = 0.047). CONCLUSIONS: Our findings may indicate that p53 alterations are not necessarily a late event in endometrial endometrioid carcinogenesis. Since a large proportion of tissues adjacent to endometrial carcinoma do not show p53 alterations, other early cellular events may also play a role.     

Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma

Abstract. Lundgren C, Auer G, Frankendal B, Moberger B, Nilsson B, Nordström B. Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.
The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I–IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted. Image cytometry DNA ploidy ( n = 340) and expression of MIB-1 ( n = 318) and p53 ( n = 323) were studied. In univariate analysis, stage ( P < 0.001), histopathologic subtype ( P < 0.001), degree of differentiation ( P < 0.001), HRT ( P = 0.034), DNA ploidy ( P < 0.001), and p53 ( P < 0.001) were significant predictors of relapse. Patient age showed that the estimated mean risk of relapse increases with nearly 64% per decade in life ( P 0.003), and the MIB-1 expression with 21% per 10-unit increment ( P 0.004). In multivariate analysis, degree of differentiation, MIB-1, and p53 lost their prognostic capability. However, after stage and histopathologic subtype, image cytometry DNA ploidy was the strongest predictor of outcome and was of value in predicting the risk for relapse. The combination of DNA ploidy, MIB-1, and p53 expression was an even stronger predictor of relapse-free survival than the individual prognostic factors.     

p53 is correlated with low BMI negative progesterone receptor status and recurring disease in patients with endometrial cancer

Objective

P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer.

Methods

40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue samples was used. Western blot was performed for detection of p53 and phospho-p53. Clinical and pathological parameters were obtained from medical records. Statistical analysis was performed using the log-rank test, the Mann-Whitney test for two independent groups and the Fisher’s exact test for dichotomous groupings.

Results

In 17.5% of the patients with endometrial cancer a p53 overexpression could be evaluated. There was a correlation between a p53 overexpression and recurring disease (p: 0.014), a negative progesterone receptor status (p: 0.021) and a low BMI (p: 0.022). Only one of 40 patients had a phospho-p53 expression.

Conclusion

Western blot is a valid method for the detection of p53 overexpression. As other authors described before, p53 overexpression seems to correlate with negative prognostic factors. The correlation between p53 overexpression and a low BMI may underline the relationship between p53 alterations and biological aggressive endometrial carcinomas.     

Prognostic value of p53 expression in stage IB1 cervical carcinoma

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.