Cyclooxygenase-2 and p53 expressions in endometrial cancer.

Cyclooxygenase-2 (COX-2) has been known to be related with various types of carcinoma, but we have insufficient knowledge about the association between COX-2 and endometrial cancer. Many have reported a close relationship between p53 expression and a poor prognosis in endometrial cancer, but it is unclear whether p53 is an independent prognostic factor. To clarify these uncertainties, we examined the expressions of COX-2 and p53 in endometrial cancer tissues. The study was carried on 152 endometrial cancer patients who had operation at Seoul National University Hospital. Paraffin-embedded tissue blocks were sectioned and immunostained using monoclonal anti-COX-2 and anti-p53 antibodies. Twenty-seven (17.8%) specimens stained as COX-2 positive. COX-2 positivity was more frequently observed in postmenopausal patients than in premenopausal patients (8.8% versus 25.0%; P = 0.009). However, COX-2 positivity did not show a statistically significant association with any other clinicopathologic characteristic (parity, body mass index, histotype, International Federation of Gynecology and Obstetrics stage, grade, lymph node metastasis, deep myometrial invasion, or p53 overexpression). Thirty-one (20.4%) specimens showed p53 overexpression and this was significantly correlated with an advanced stage (P = 0.001), poor differentiation (P < 0.001), lymph node metastasis (P = 0.012), and deep myometrial invasion (P < 0.001). Multivariate Cox regression analysis showed that advanced stage was an independent prognostic factor of survival, but p53 overexpression was not. COX-2 may be associated with endometrial cancer carcinogenesis during the postmenopausal period but not with tumor aggressiveness and p53 overexpression. The p53 overexpression was found to be strongly associated with endometrial cancer aggressiveness.     

血管生成拟态在子宫内膜癌组织中的表达及意义

目的:探讨血管生成拟态（v asculogenic mimicry,VM）在子宫内膜癌中的表达及其与临床病理特征和预后的关系。方法:收集解放军白求恩国际和平医院2005年1 月至2014年6 月术后随访资料完整的子宫内膜癌标本267 例,采用CD31/PAS双重染色鉴定VM结构,分为VM阳性组与VM阴性组,免疫组织化学SP法检测CD133 的表达。结果:267 例子宫内膜癌患者中65例（24.3%）存在VM。VM的形成与子宫内膜癌FIGO分期（χ2= 9.987 ,P = 0.002）,组织学分级（χ2= 11.795 ,P = 0.001）,肌层浸润深度（χ2= 5.499,P = 0.019）,脉管内有无癌栓（χ2= 22.599,P < 0.001）及淋巴结有无转移（χ2= 7.848,P = 0.005）密切相关。Kaplan-Mei er法生存分析发现VM阳性组生存时间（中位生存时间为51个月）明显低于VM阴性组（中位生存时间为100 个月）,二者比较差异具有统计学意义（χ2= 70.973,P < 0.001）。 CD133 在VM阳性组的表达率为75.4%（49/ 65）,较VM阴性组58.9%（119/ 202）高,二者比较差异具有统计学意义（χ2= 5.720,P = 0.017）。 结论:VM与子宫内膜癌的发生、发展及恶性度密切相关,是影响患者预后的重要指标,CD133 表达阳性的肿瘤干细胞可能参与子宫内膜癌VM的形成。      

Expression of cyclooxygenase-2 and inducible nitric oxide synthase correlates with tumor angiogenesis in endometrial carcinoma

The present study evaluated the significance of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in 30 patients with endometrial carcinoma and the relationship of those molecular markers to tumor characteristics and microvessel density (MVD). Immunohistochemical expression of COX-2, iNOS, and CD34 was analyzed on paraffin-embedded tissue sections. The COX-2 and iNOS positive rates were 66.7% and 73.3%, respectively. The level of COX-2 expression was higher in grade II tumors than in grade III tumors (p < 0.05). The percentage of iNOS positivity was higher in patients with deep myometrial invasion than in patients without or less than 50% myometrial invasion (p < 0.05). There was significant correlation between positive COX-2 and positive iNOS expression (r = 0.601, p < 0.001). Both COX-2 and iNOS were significantly correlated with MVD (r = 0.02 p < 0.05; r = 0.599 p < 0.0001, respectively). The present findings suggest that combined expression of COX-2 and iNOS may play an important role in development and invasion of endometrial cancer and that this could be partially attributable to modulation of angiogenesis by COX-2 and iNOS.     

PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy

The prognostic significance of PTEN expression in endometrial carcinoma has not been clear. We conducted the present study to clarify the relationship between PTEN expression and prognosis in advanced endometrial carcinoma. Of 784 patients with endometrial carcinoma who underwent primary treatment between 1985 and 2000 at 5 institutions, 98 pure endometrioid carcinomas with retroperitoneal lymph node metastasis were provided for our study. PTEN expression was determined by immunohistochemic staining. Negative or mixed PTEN staining was observed in 64 (65.3%) patients. The survival rate for PTEN-positive patients was significantly higher than that for PTEN-negative or -mixed patients. PTEN-staining status was not associated with patient age, International Federation of Gynecology and Obstetrics (FIGO) stage, myometrial invasion or histologic grade. Of the 98 patients, 87 received radiation therapy (n = 25) or chemotherapy (n = 62) after surgery. PTEN expression did not relate to survival for patients receiving radiation therapy. In contrast, the survival rate for PTEN-positive cases was significantly higher than that for PTEN-negative or -mixed cases when patients underwent chemotherapy (62.4% vs. 11.8%). Subsequent multivariate analysis revealed that PTEN staining was an independent prognostic factor for patients undergoing chemotherapy. PTEN-positive staining was a significant prognostic indicator of favorable survival for patients with advanced endometrial carcinoma who underwent postoperative chemotherapy.     

The significance of the amount of myometrial invasion in patients with Stage IB endometrial carcinoma

BACKGROUND: The 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma defined Stage IB as disease with invasion of less than one-half of the myometrium, although most of the data on prognostic factors are based on invasion of the inner one-third, middle one-third, or outer one-third of the myometrium. The objective of this study was to determine whether the depth of myometrial invasion is correlated with outcome in patients with Stage IB endometrial carcinoma. METHODS: Between November, 1987 and June, 1998, 251 patients with Stage IB endometrioid adenocarcinoma of the uterus underwent simple hysterectomy followed by intravaginal brachytherapy. The depth of myometrial invasion was less than or equal to one-third (Group I) in 191 of 251 patients (79%) and greater than one-third to less than one-half (Group II) in 52 of 251 patients (21%). Comprehensive surgical staging (CSS) was done in 12% of patients. The two groups were balanced with regard to age (< 60 years vs. > or = 60 years), FIGO grade, lower uterine segment involvement (LUSI), CSS, and the use of postoperative external-beam radiation. The rate of capillary-like space invasion (CLSI), however, was 9% in Group I compared with 25% in Group II (P = 0.002). The median follow-up was 58 months. RESULTS: The overall 5-year actuarial local-regional control (LRC), disease free (DFS) survival, and overall survival (OS) rates were 95%, 92%, and 92%, respectively. These end points, however, did not vary significantly between the two groups. The 5-year LRC, DFS, and OS rates in Groups I and II were 96% versus 95%, respectively (P = 0.9); 92% versus 94%, respectively (P = 0.7); and 92% versus 90%, respectively (P = 0.5). On multivariate analysis, the influence on outcome of age, grade, amount of myometrial invasion, LUSI, and CLSI was evaluated. Only age > or = 60 years and FIGO Grade 3 were correlated with poor DFS (P = 0.02 and P = 0.03, respectively) and OS (P = 0.001 and P = 0.01, respectively). CONCLUSIONS: Based on this study, in patients with Stage IB endometrial carcinoma, the amount of myometrial invasion, defined as invasion less than or equal to one-third of the myometrium versus invasion greater than one-third and less than one-half of the myometrium, did not appear to influence outcome. Age > or = 60 years and FIGO Grade 3, however, emerged as independent prognostic factors for poor DFS and OS.     

Is endometrial carcinoma intrinsically more aggressive in elderly patients?

BACKGROUND: The current study was conducted to determine the influence of old age (age >/= 70 years) on outcome in a group of patients with endometrial carcinoma who were treated with simple hysterectomy followed by adjuvant radiation therapy (RT). METHODS: Between November 1987 and May 2000, 405 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB-II endometrial carcinoma were treated with postoperative RT. Intravaginal RT alone was given to 77% of patients (median dose, 21grays [Gy] given in 3 fractions). Additional postoperative external beam radiation therapy (EBRT) was given to 23% of patients (median dose, 45 Gy). Eighty-four patients were age >/= 70 years and 321 patients were age < 70 years. The two groups were well balanced with regard to race, comprehensive surgical staging, aggressive histology, lymphovascular invasion, lower uterine segment involvement, cervical involvement, and the use of postoperative EBRT. Significantly more patients in the age >/= 70 years group had other comorbidities such as obesity, diabetes mellitus, or hypertension (P = 0.02) and were found to have deep (> 50%) myometrial invasion (P = 0.008). RESULTS: With a median follow-up time of 48 months, the 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were 95%, 91%, and 90% respectively. On multivariate analysis, poor LRC was found to be correlated with age >/= 70 years (P = 0.019) and lymphovascular invasion (P = 0.001). Poor DFS was found to be correlated with age >/= 70 years (P = 0.03), lymphovascular invasion (P = 0.01), and aggressive histology (P = 0.001). Similarly, poor OS was found to correlate with age >/= 70 years (P = 0.001), lymphovascular invasion (P = 0.01), aggressive histology (P = 0.01), and cervical involvement (P = 0.02). The same factors that were found to correlate with OS (age >/= 70 years, lymphovascular involvement, aggressive histology, and cervical involvement) also appeared to correlate with disease-specific survival (P = 0.03, P = 0.008, P = 0.001, and P = 0.04, respectively). The 5-year actuarial rates of Radiation Therapy Oncology Group late complications that were >/= Grade 3 (gastrointestinal tract, genitourinary tract, or vagina) were 3% in both groups. CONCLUSIONS: Even when treated in a similar fashion, endometrial carcinoma patients age >/= 70 years appear to fare worse than younger patients independent of other poor prognostic factors. The rate of complications from adjuvant RT, despite a higher rate of comorbidity in elderly patients, was found to be similar in both age groups. Endometrial carcinoma appears to be intrinsically more aggressive in older patients, thus mandating further improvement in their treatment strategies.     

Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival.

PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.     

Long-term outcome in endometrial carcinoma favors a two- instead of a three-tiered grading system

PURPOSE: Endometrial carcinoma is the most common malignancy of the female genital tract. Recognized prognostic factors include FIGO stage, histologic grade, depth of myometrial invasion, and age. Although determination of these factors may seem clear and reproducible, the histologic grade has recently been the subject of debate. A retrospective analysis of long-term outcome and predictive factors in endometrial carcinoma was conducted, focusing on the prognostic value of tumor grade. MATERIALS AND METHODS: The study included 253 patients with endometrial carcinoma Stages I to III, who were treated between 1984 and 1993. The histologic slides were reviewed and the prognostic value of stage, age, myometrial invasion (depth and pattern), tumor grade, and histologic subtype was analyzed. The end point was cancer-specific death; the median follow-up time was 11.7 years. RESULTS: The actuarial 5- and 10-year cancer-specific survival rates (CSS) were 85% and 82%, respectively. Five-year vaginal and/or pelvic recurrence and distant relapse rates were 7% and 15%. In multivariate analysis, stage, pattern of myometrial invasion, tumor grade, and age were independent prognostic factors. At pathology review, a shift from Grade 2 to Grade 1 was seen in 112 of the original 144 Grade 2 (78%). There was no difference in CSS between Grade 1 and Grade 2 (94 vs. 90% for original grade and 92 vs. 95% for grade after review), whereas Grade 3 was found to be a significant adverse prognostic factor (p < 0.001). CONCLUSIONS: The independent prognostic factors for patients with endometrial cancer were stage, pattern of myometrial invasion, tumor grade, and age. Systematic grading led to a considerable shift from Grade 2 to Grade 1. However, there was no difference in prognostic significance between Grade 1 and 2, whereas Grade 3 was a major adverse prognostic factor. A two-tiered grading system, instead of the currently used three-tiered system seems preferable, because it has a better correlation with clinical outcome and is expected to have less interobserver variability.     

Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus

BACKGROUND: The purpose of this study was to determine clinicopathologic variables associated with extrauterine disease, recurrence, and survival in patients with carcinosarcoma (CS) of the uterus. METHODS: Patients believed to have disease confined to the uterine corpus who underwent primary surgical assessment were identified and data retrospectively reviewed. RESULTS: Occult metastases were found in 38 (61%) of 62 patients. At last follow-up, 31 (50%) had had recurrence, with an extrapelvic component in 43%, and 53% had died. Depth of myometrial invasion and lymph-vascular space invasion (LVSI) were associated with extrauterine disease. Five-year survival for patients with disease confined to the corpus (74%) was significantly greater than for those with more advanced disease (24%, P = 0.0013). Factors associated with recurrence and survival included depth of myometrial invasion, LVSI, adnexal and serosal involvement, positive cytology, and lymph node metastases. Of 24 patients with uterine disease only, 11 received no adjuvant therapy, yet 8 (73%) were free of disease at last follow-up. Neither adjuvant radiotherapy nor chemotherapy was identified as an independent prognostic variable for recurrence or survival. CONCLUSIONS: More than half of patients with CS clinically confined to the uterine corpus harbor occult metastases in a pattern similar to that found with endometrial carcinoma. Survival is significantly diminished for this group. Although the benefit of adjuvant therapy cannot be demonstrated by this study, a number of early stage patients survive without adjuvant therapy. This argues for extending the International Federation of Gynecology and Obstetrics endometrial carcinoma surgical staging system to include CS, and also for conducting prospective trials to examine the benefits of adjuvant therapy for patients with early stage disease.     

Stage I serous papillary carcinoma of the endometrium

From 1973 to 1987, 16 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I serous papillary endometrial carcinoma were evaluated and treated at the University of Kentucky Medical Center (Lexington, KY). All patients were 60 years of age or older, and all were postmenopausal. Patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling, and 38% were noted to have more extensive disease than appreciated clinically. Nine patients were given adjuvant postoperative radiation. Seven patients (44%) developed recurrent cancer with liver, lung, and upper abdomen being the most common sites of spread. Prognosis was most directly related to the presence of lymph vascular space invasion and the depth of myometrial penetration. No patient with serous papillary carcinoma confined to the endometrium developed recurrent cancer. In contrast, the recurrence rate of patients having myometrial invasion was 70% (P less than 0.03). Hormonal therapy was of limited value in the treatment of recurrent disease. This data suggests the need for adjuvant systemic therapy in the treatment of patients with Stage I serous papillary carcinoma of the endometrium who have myometrial invasion.     

原发性子宫内膜癌血清PON-1活性及Q192R基因多态性的检测及临床意义

目的:探讨血清中对氧磷酶-1(paraoxonase-1,PON-1)的表达活性及PON-1Q192R基因多态性与原发性子宫内膜癌的相关性。方法:选取2019年01月至2020年10月于我医院就诊的30例子宫内膜腺癌、30例子宫内膜非典型增生和30例正常子宫内膜患者为研究对象,检测3组入选者血清PON-1对有机磷脂酶、芳香脂酶、同型半胱氨酸硫内酯酶活性及Q192R表型,分析3组患者血清PON-1的表达活性差异、Q192R基因表达差异和子宫内膜癌组不同病理分级分期PON-1活性差异。探讨血清中PON-1活性、Q192R基因多态性与子宫内膜癌的相关性。结果：三组患者的一般情况无差异。子宫内膜癌组患者血清中PON-1对有机磷脂酶、芳香脂酶及同型半胱氨酸硫内酯酶的活性表达明显低于子宫内膜不典型增生组及正常子宫内膜组患者,其差异有统计学意义(P<0.05)。血清PON-1活性的降低与子宫内膜癌FIGO分期、分化程度、肌层浸润深度及淋巴结转移相关,其差异有统计学意义(P<0.05),血清PON-1活性与子宫内膜癌病理类型及宫颈受累情况无关(P> 0.05)。正常子宫内膜组的Q19...     

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n = 80) was immunohistochemically scored as four groups (IDO-, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P = 0.002 and P = 0.001, respectively) compared to patients with no or weak expression of IDO (IDO- or 1+). The 5-year PFS for IDO-/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n = 64), the PFS for IDO2+/3+ was significantly poor (P = 0.001) compared to that for IDO-/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P = 0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.     

环氧化酶-2在子宫内膜样腺癌中的表达及其与PTEN的相关性

 目的 研究环氧化酶-2（COX-2）在子宫内膜样腺癌（EAC）中的表达及意义，探讨COX-2与PTEN的相关性。方法 用免疫组化SP法检测COX-2、PTEN在正常子宫内膜、子宫内膜非典型增生及EAC中的表达。结果 COX-2的阳性表达率自正常内膜至非典型增生及EAC呈阶梯性升高（13.33 %、50.00 %、64.58 %）（P＜0.05）。EAC中，COX-2蛋白表达与组织分级（G1、G2、G3分别为4／9、64.29 %、81.82 %）、肌层浸润（深肌层浸润、浅肌层浸润分别为75.00 %、57.14 %）、手术-病理分期（早期、晚期分别为56.41 %、9／9）、淋巴转移（有、无分别为9／9 、56.41 %）相关（P = 0.007，P = 0.009，P = 0.001，P = 0.001）。预后好的EAC中，COX-2与 PTEN之间存在负相关（rs = -0.400，P＜0.05）。结论 COX-2与EAC的浸润转移相关；预后好的EAC中，PTEN可能参与COX-2的表达调控。     

子宫内膜癌中FasL和Ki67的表达及临床意义

目的:检测子宫内膜癌组织中脂肪酸合成酶配体（fatty acid synthase ligand，FasL）和细胞增殖核抗原（Ki67）的表达情况，探讨二者表达的相关性及临床意义。方法:搜集2012年6月至2015年8月在我院确诊并治疗的82例子宫内膜癌标本作为研究对象，同期选取24例非典型增生子宫内膜标本和30例正常子宫内膜标本作为对照。采用免疫组化法检测不同子宫内膜组织中Ki67、FasL蛋白表达水平，分析Ki67、FasL与子宫内膜癌各项临床病理参数的相关性。采用Spearman对Ki67与FasL的相关性进行分析。结果:Ki67、FasL在正常子宫内膜、非典型增生内膜及子宫内膜癌组织中阳性率均逐渐增加，两两比较差异有统计学意义（P<0.05）。Ki67、FasL表达与子宫内膜癌患者FIGO分期、病理分级、淋巴结转移及肌层浸润密切相关(P<0.05)，与患者年龄、月经状态、脉管瘤栓形成无明显相关性（P>0.05）。经Spearman相关性分析，子宫内膜癌组织中Ki67与FasL表达呈正相关性（r=0.438，P<0.05）。Ki67高表达者2年存活率明显低于低表达者（61.76% vs 92.86%，P<0.05）；FasL高表达者2年存活率明显低于低表达者（57.14% vs 88.46%，P<0.05）。结论:Ki67、FasL在子宫内膜癌组织中显著高表达，有望共同作为诊断子宫内膜癌及判断患者预后的有效生物标志物。     

Cyclooxygenase-2 expression in lymph node metastasis of cervical and vulvar cancer

Overexpression of cyclooxygenase-2 (COX-2), characterizes tumors with high potential for local invasion and lymph node involvement. We investigated the expression of COX-2 in primary tumors and metastatic regional lymph nodes (TDL) from untreated and chemotherapy treated cervical cancer, as well as vulvar cancer. Immunostaining of COX-2, expressed as values of COX-2 intensity density (COX-2 IDV) was performed on 57 metastatic TDL and 24 corresponding primary rumors from 14 cervical and 9 vulvar cancer patients admitted to the Department of Obstetrics and Gynecology, Catholic University of Rome. In 6 locally advanced cervical cancer tissue samples, from both primary tumor and TDL, were obtained after chemotherapy treatment. In untreated cervical cancer, COX-2 IDV in tumor cells from positive TDL were significantly lower (median 0.69, range 0.22-0.92) than those from primary tumors (median = 3.84, range 0.19-7.67) (p=0.011). In cervical cancer exposed to chemotherapy, COX-2 IDV in tumor cells from positive TDL were significantly lower (median = 2.06, range 1.48-6.52) than those from primary tumors (median = 6.4, range 4.5-13.7) (p=0.037). In vulvar cancer COX-2 IDV in tumor cells from positive TDL were lower (median = 0.39, range 0.02-6.09) than those from primary tumors (median = 2.49, range 0.71-8.10) (p=0.04). In conclusion, we showed that COX-2 expression is down-regulated in cervical and vulvar tumor cells invading the regional lymph nodes with respect to primary tumors, thus emphasizing the need for deeper insight into the tissue specific relation between tumor cells and node microenvironment.     

Peritoneal fluid cytology in endometrial cancer: its significance and the role of chromic phosphate (32P) therapy

Between 1978 and 1986, 243 patients (all stages) had peritoneal fluid cytology performed while undergoing total abdominal hysterectomy for endometrial carcinoma; 39 (16%) were found to be positive. At 3 years (median follow-up of 30 months) the disease-free survival (DFS) for the 165 negative cytology clinical Stage I patients was 91% compared to only 56% for the 25 positive cytology patients (p less than .001). Of the 25 Stage I positive cytology patients, 14 with greater than one-third myometrial invasion had a DFS of 30% at 3 years as compared to 87% for negative cytology patients with comparable depth of invasion (p less than .001). There was no difference in DFS between the negative and positive cytology Stage I patients who had one-third or less myometrial invasion. Stage I patients with histologic Grade 2 and 3 had a lower 3 year DFS when cytology positive, 49% and 22%, versus 92% and 79% when cytology negative (p less than .001 and p = .03 respectively). In clinical Stage II patients the 3-year DFS was 21% for those with a positive cytology and 59% with a negative cytology. Fourteen of the 25 clinical Stage I positive cytology patients received 15 mCi of intraperitoneal 32P. At 3 years they had a 68% DFS as compared to 27% for those not receiving 32P (p = 0.01). All 11 patients with superficial myometrial invasion (9 received 32P) remained disease-free. The 4 Stage I patients with deep invasion who received 32P therapy had an improvement in abdominal/pelvic control and DFS when compared to 9 similar patients who did not receive 32P (p = .02). For histologic Grade 2 and 3 patients, there was a 64% 3-year DFS in the 32P treated group and 16% for those not receiving 32P (p = 0.02). Although 32P therapy improved DFS in Stage I positive cytology patients its use along with pelvic radiation therapy can lead to complications. Of 9 Stage I patients receiving 32P as well as pelvic irradiation, 4 experienced serious bowel complications requiring surgery. None of the 5 patients receiving 32P only had a complication.     

Analysis of prognostic factors and patterns of recurrence in patients with pathologic stage III endometrial cancer

PURPOSE: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. METHODS AND MATERIALS: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. RESULTS: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. CONCLUSIONS: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.     

Increased cyclooxygenase-2 (COX-2) expression is associated with chemotherapy resistance and outcome in ovarian cancer patients.

BACKGROUND: Cyclooxygenase-2 (COX-2) expression is associated with aggressive clinicopathological parameters and unfavourable prognosis in several human malignancies. The aim of this study was to investigate the expression of COX-2 and its association with clinicopathological parameters, response to treatment, and clinical outcome in ovarian cancer patients. PATIENTS AND METHODS: COX-2 expression was analysed by immunohistochemistry in 87 primary ovarian carcinomas from patients with measurable disease after primary laparotomy. RESULTS: COX-2 immunoreaction was observed in 39 (44.8%) cases, and did not differ in distribution according to age, FIGO stage, debulking at time of surgery, presence of ascites, histotype or tumour grade. Both in patients cytoreduced at first surgery and in those undergoing only explorative laparotomy, the percentage of COX-2 positivity was significantly higher in non-responding than in patients responding to treatment (P = 0.043 and P = 0.0018, respectively). In multivariate analysis, only COX-2 positivity and older age retained an independent role in predicting a poor chance of response to treatment. There was no significant difference of clinical outcome according to COX-2 status in patients undergoing primary debulking while, in the subgroup of patients who underwent explorative laparotomy, COX-2-positive cases showed a shorter time to progression (P = 0.025) and overall survival (P = 0.025). CONCLUSIONS: The assessment of COX-2 status could provide additional information in order to identify ovarian cancer patients with a poor chance of response to chemotherapy and potentially candidates for more individualised treatments.     

Do conventional pathologic features lose their prognostic significance following postoperative radiation therapy in pathologic stage I-II endometrial adenocarcinoma?

Recent data have suggested that conventional pathologic features (myometrial invasion (MI), grade, stage) lose their prognostic significance following postoperative radiation therapy (RT) in Stage I-II endometrial carcinoma. Our goal was to test this finding in a large cohort of women treated at our institution. Between 1980 and 1997, 188 Stage I (140) and II (48) endometrial adenocarcinoma patients received postoperative RT. RT consisted of pelvic RT (112), vaginal brachytherapy (36), or both (40). Clinicopathologic factors were evaluated as prognostic factors on both univariate and multivariate analyses. Factors correlated with recurrence on univariate analysis included MI (P = 0.05), grade (P = 0.07), lymphovascular invasion (LVI) (P = 0.001) and stage (P = 0.03). Multivariate analysis confirmed the significance of grade (P = 0.02), LVI (P = 0.001), and stage (P = 0.02). Conventional pathologic features do not lose their prognostic significance in pathologic Stage I-II endometrial adenocarcinoma patients following postoperative RT. These factors should continue to be used to identify women at risk for recurrence despite adjuvant RT. New prognostic markers are needed to better identify high-risk patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 224-230 (2000).