Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma

OBJECTIVE: To evaluate the significance of the expression of HER-2/neu as a prognostic factor, we retrospectively examined its overexpression rates chiefly in ovarian clear cell adenocarcinoma (CCA) and their relationships with FIGO stage, lymph node metastasis, and prognosis. METHODS: In addition to 90 specimens of CCA (stage I, 52; stage II, 7; stage III, 28; stage IV, 3) obtained between 1987 and 2002, 19 specimens of serous adenocarcinoma (S), 19 specimens of mucinous adenocarcinoma (M), and 19 specimens of endometrioid adenocarcinoma (E) collected at initial surgery were studied. The expression of HER-2/neu was immunohistologically scored on a scale of 0 to 3+ according to the HercepTest scoring system, and 2+ and 3+ were regarded as overexpression. The relationship between HER-2/neu overexpression and outcome was evaluated by the Kaplan-Meier method and the log-rank test. The relationship with advanced-stage cancer was analyzed by Fisher's exact test. The relationships with lymph node metastasis and histologic types were compared by the t test. RESULTS: The rate of HER-2/neu overexpression in CCA was 45.6% (0, 1+, 2+, and 3+ in 14, 35, 36, and 5 cases, respectively), and no differences in the overexpression rate were noted among histologic types: 52.7% in S, 42.1% in M, and 26.4% in E. In CCA, no association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.5708), FIGO stage (P = 0.5147), or lymph node metastasis (P = 0.3624). CONCLUSION: The absence in CCA of an association between HER-2/neu overexpression and outcome, stage, or lymph node metastasis indicates that HER-2/neu overexpression is not a prognostic risk factor.     

Proliferative activity of early ovarian clear cell adenocarcinoma depends on association with endometriosis

OBJECTIVE: To investigate differences in the biological characteristics of ovarian clear cell adenocarcinoma based on the presence/absence of endometriosis and tumor proliferative activity. METHODS: Stage I ovarian clear cell adenocarcinoma patients were divided into groups with and without endometriosis, and immunohistochemical expression of proliferating cell nuclear antigen was determined in surgical specimens. Then xenograft models of human ovarian clear cell adenocarcinoma with or without human ectopic endometrium were created in severe combined immunodeficiency mice, and tumor growth was assessed from the wet weight and the bromodeoxyuridine uptake. Furthermore, a xenograft model of human endometriosis was made with or without ovarian clear cell adenocarcinoma and cytokine production was investigated. RESULTS: The proliferating cell nuclear antigen labeling index was significantly lower in the tumors of patients with endometriosis compared to the tumors of patients without endometriosis. In tumor-bearing mice, the tumor weight and bromodeoxyuridine uptake were both significantly lower when ovarian clear cell adenocarcinoma was associated with endometriosis than in its absence. Release of transforming growth factor-beta1 and interleukin-6 from the ectopic human endometrium was greater in the presence of clear cell adenocarcinoma than without it, and transforming growth factor-beta1 levels showed a significant difference. CONCLUSION: The proliferative activity of early ovarian clear cell adenocarcinoma seems to depend on the association of this cancer with endometriosis. When endometriosis is associated with ovarian clear cell adenocarcinoma, there is a change of its cytokine production that may inhibit tumor growth.     

A heavily pretreated patient with recurrent clear cell adenocarcinoma of the ovary in whom carcinomatous peritonitis was controlled successfully by salvage therapy with gemcitabine

Introduction  Advanced clear cell adenocarcinoma of the ovary is a histologic type with an extremely poor prognosis. No reports have been published concerning useful drugs for salvage chemotherapy for this type of cancer. We performed salvage therapy with gemcitabine in a patient with multiple-drug- resistant, unresectable recurrent clear cell adenocarcinoma of the ovary and succeeded in stabilizing recurrent lesions and controlling carcinomatous peritonitis. Case report  A 55-year-old woman was in Stage IIIc of clear cell adenocarcinoma of the ovary. She had recurrent tumors after primary cytoreductive surgery, which were unresectable and also resistant to paclitaxel, carboplatin, irinotecan, and oral etoposide. After three courses of fourth-line chemotherapy with gemcitabine for the treatment of carcinomatous peritonitis and hepatic and splenic metastatic lesions, serum CA-125 and the severity of ascites showed marked decreases, and its efficacy for the hepatic and splenic metastatic lesions was classified as 5-month stable disease. The toxicity of this drug was in the acceptable range. Conclusion  Gemcitabine is also useful for heavily pretreated clear cell adenocarcinoma of the ovary. It is necessary to consider the use of drugs without cross resistance to platinum and taxanes in the selection of drugs for this cancer. An erratum to this article can be found at     

Prognostic determinants in patients with uterine and ovarian clear cell carcinoma: A SEER analysis

Introduction

The purpose of this study is to analyze and compare the demographics, treatment, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC).

Methods

The Surveillance, Epidemiology and End Results (SEER) program data for all 18 registries from 1988 to 2010 was reviewed to identify women with OCCC and UCCC. Demographic and clinical data were compared, and the impact of tumor site on survival was analyzed using the Kaplan–Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model.

Results

The final study group consisted of 5421 women with clear cell histopathology. 3631 (67%) had OCCC and 1790 (33%) had UCCC. The mean age at diagnosis was 56 (± 12) years for women with OCCC and 67.7 (± 12.0) years for UCCC (P < 0.001). Patients with OCCC had a higher rate of late stage disease (38.9% vs. 21.2%; P < 0.001). Over the entire study period, after adjusting for known variables, there was no significant difference in cancer specific mortality between UCCC and OCCC, HR 1.05 (0.92–1.19). In the subset analysis by staging, in women with localized disease there was an improved survival in UCCC compared to OCCC. In contrast, in women with distant disease there was an increased mortality in women with UCCC.

Conclusion

In the entire population, there was no significant difference in cancer related mortality between the groups. However, in women with localized disease, UCCC had improved survival, but increased mortality in distant disease compared to OCCC.     

Paclitaxel–platinum combination chemotherapy for advanced or recurrent ovarian clear cell adenocarcinoma: a multicenter trial

The therapeutic effect of a combination of paclitaxel (PTX) and platinum (PLT) in ovarian clear cell adenocarcinoma (CC) patients with measurable disease has yet to be elucidated. In this study, we used retrospective review to evaluate the results of treatment with a combination of PTX and PLT in CC patients with measurable disease. A total of 28 patients with measurable residual CC (15 cases with primary disease, 13 cases with recurrent disease) treated with combination PTX-PLT chemotherapy was identified through medical records from ten institutions. Clinical response to chemotherapy was evaluated using Response Evaluation Criteria in Solid Tumors criteria. Of the 28 cases, 8 of 15 patients with primary disease (53.3%) and 3 of 13 patients with recurrent disease (23.1%) responded to PTX-PLT chemotherapy. The response rate for cases with late recurrent disease (>12 months) was 20% (1/5), whereas the rate was 25% (2/8) for cases with early recurrent (<12 months) or refractory disease. Our results indicate that the combination of PTX and PLT may have greater efficacy against CC than conventional PLT-based chemotherapy that does not include PTX.     

Endobronchial clear cell adenocarcinoma occurring in a patient 15 years after treatment for DES-associated vaginal clear cell adenocarcinoma

BACKGROUND: Clear cell adenocarcinoma (CCA) of the vagina and cervix in young women is associated with prenatal exposure to diethylstilbestrol (DES). Parenchymal pulmonary metastases are known to occur following treatment of the primary tumor. Most recurrences present within 2 to 3 years of the initial diagnosis. CASE: This is a case report of a solitary endobronchial clear cell adenocarcinoma occurring 15.3 years after the initial diagnosis of DES-induced CCA. CONCLUSIONS: This case suggests that management of clear cell cancer survivors should involve long-term follow-up because of the potential for the appearance of a new focus of clear cell adenocarcinoma.     

Clinical manifestations in patients with ovarian clear cell carcinoma with or without co-existing endometriosis

Objectives. The symptoms associated with ovarian cancer are vague. Endometriosis, which causes dysmenorrhea and dyspareunia, is frequently detected along with ovarian clear cell carcinoma (OCCC). We have therefore evaluated the clinical manifestations of OCCC based on the co-existence of endometriosis.

Methods. A retrospective analysis was conducted on 43 patients who had been treated for OCCC at the National Cancer Center between June 2000 and July 2007. Using medical records and the cancer registry, the clinical features and laboratory findings were analysed.

Results. Endometriosis was identified in 16 (37.2%) of the 43 patients with OCCC. The main presenting symptoms included a hard, palpable mass (32.6%), and newly developed or an exacerbation of dysmenorrhea (32.6%) and dyspareunia (25.6%). Gastrointestinal symptoms, pelvic pain, and abdominal distension existed in nine (20.9%), eight (18.6%) and one (2.3%) of the patients, respectively. The symptoms did not differ statistically in patients with or without endometriosis. Thirty-seven percent (11/30) of the patients had a normal CA-125 level (<35 U/ml); 18.8% (3/16) of the patients without endometriosis and 57% (8/14) of the patients with endometriosis had normal levels of CA-125 (<35 U/ml). Nine of 16 (56.3%) patients with early stage OCCC had a normal CA-125 level.

Conclusions. The main presenting symptoms in patients with OCCC include a hard, palpable mass, dysmenorrhea and dyspareunia, irrespective of co-existing endometriosis. A normal CA-125 level has limited value in excluding OCCC, especially in the early stages.     

A case of persistent endometriosis after total hysterectomy with both salpingo-oophorectomy managed by radiation therapy

Persistent endometriosis after total hysterectomy and both salpingo-oophorectomy (TH with BSO) is a rare condition and the etiology is uncertain. The exact incidence of persistent endometriosis after definitive surgery is not known. In addition, the treatment of persistent endometriosis after complete surgical excision is controversial. We report a case of persistent endometriosis with vaginal and sigmoid-colonic invasion after TH with BSO. The lesions were not responsive to hormonal therapy. The patient was managed successfully by therapeutic pelvic radiation. Received: 26 October 2000 / Accepted: 12 December 2000     

Cytologic examination to detect clear cell adenocarcinoma of the vagina or cervix

OBJECTIVE: The aim of this study was to determine the sensitivity of cytopathologic examination for the detection of vaginal or cervical clear cell adenocarcinoma (CCA). METHODS: Systematic collection in the Dutch automated nationwide pathology archive of all cytology and histology data of women with CCA, born in The Netherlands after 1947 was performed. All cytologic examinations within 2 years prior to histological diagnosis of CCA were included. RESULTS: Ninety patients with CCA have been registered. Forty-nine of these patients had cytologic examinations prior to histology. Eighty-five percent of cervical CCAs were preceded by a positive cervical smear. One hundred percent of vaginal CCAs were preceded by a positive vaginal smear. Cervical smears are relatively insensitive to detect vaginal CCA. Vaginal smears were often omitted. Only 2 apparently false-negative smears were found. The mean numbers of smears in diethylstilbestrol (DES)-exposed and nonexposed women were minimally different: 1.0 and 0.8, respectively. This suggests an only modest impact of the awareness of DES as a risk factor. FIGO tumor stage I was preceded more frequently by cytology than the higher tumor stages. CONCLUSION: The majority of CCA cases can be detected at an early stage by yearly clinical and cytological examinations, which must comprise cervical as well as vaginal sampling. Since CCA may also occur in postmenopausal women, for the purpose of secondary prevention of CCA regular cytologic examinations of DES-exposed women must be continued after menopause.     

Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival

Objectives

To determine the impact of venous thromboembolism (VTE) during primary treatment of ovarian clear cell carcinoma (OCCC) on survival.

Methods

After Institutional Review Board approval, 74 cases of OCCC were retrieved from our pathology files. Clinical and pathological data were obtained by medical record and pathology review. Standard statistical analyses were performed.

Results

Among 74 patients with OCCC, VTE was diagnosed in 11 (15%) during primary treatment and 7 (9%) at time of cancer recurrence. 56 (76%) patients never developed VTE. Patients with VTE during OCCC primary treatment had shorter progression-free survival (PFS) and overall survival (OS) than OCCC patients without VTE (median PFS 11 vs. 76 months, p = 0.01, median OS 19 vs. 90 months, p = 0.001). Patients with VTE during OCCC primary treatment had a 3.9-fold increase in risk of recurrence (p = 0.007) and a 6.3-fold increase in risk of death (p < 0.001). After controlling for cancer stage, VTE during OCCC primary treatment remained an independent prognostic factor for death (HR = 3.6, p = 0.005). No patient died of VTE.

Conclusions

VTE during OCCC primary treatment is associated with a significantly higher risk of cancer recurrence and death. This increased risk is not attributable to VTE-related mortality and raises the possibility that a paracrine circuit involving thrombosis might contribute to a more aggressive tumor biology.     

Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma

OBJECTIVE: The purpose of this study was to report the results of adjuvant CPT-11 and MMC combination chemotherapy (CPT-M) for ovarian clear cell adenocarcinoma (OCCA). METHODS: Between 1996 and 2002, 20 patients with OCCA underwent primary debulking surgery and received 6 treatments of CPT-11 (140 mg/m2) in combination with MMC (7 mg/m2), 2 weeks apart with a space of 3-4 weeks between the 3rd and 4th treatment in adjuvant setting. Overall survival was compared with our historical control treated between 1983 and 1995, in which 14 patients with OCCA were treated with an initial optimal standard surgery and postoperative adjuvant cyclophosphamide, doxorubicin, and cisplatin (CAP) combination chemotherapy. RESULTS: Median age was 51 years old (range, 29-74). Twelve patients were in stage Ic, 1 in stage IIa, 5 in stage IIc, 1 in stage IIIc, and 1 in stage IV. Optimal cytoreduction with standard surgery was obtained in all 20 patients. The major toxicity with this regimen was neutropenia, which was reversible. The incidences of grade 3 and 4 neutropenia were 25% and 15%, respectively. The non-hematological toxicities were generally mild and well tolerated. One patient with stage Ic refused chemotherapy after the first cycle of CPT-M, and died of her disease 8 months after initial surgery. Five-year survival rate was 95.0% for CPT-M group, and 63.5% for CAP group (P = 0.042). Survival was significantly better for patients treated with CPT-M. CONCLUSION: This preliminary study shows that the combination of CPT-M appears to be safe and useful in patients with OCCA. Prospective randomized trials should be conducted to assess this regimen appropriate for women with OCCA.     

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

BACKGROUND: Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease). METHODS: Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup. RESULTS: Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P=0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH=0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P=0.557). CONCLUSIONS: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.     

卵巢恶性肿瘤患者手术后激素治疗对其预后影响的初步探讨

目的 探讨卵巢恶性肿瘤患者手术后激素治疗(HT)对其预后及相关因素的影响.方法 对31例卵巢恶性肿瘤患者(HT组)手术后使用结合雌激素或尼尔雌醇加甲羟孕酮作为HT,同时选择同期收治的年龄、临床期别和病理类型大致相同的44例卵巢恶性肿瘤患者(非HT组)作为对照.采用免疫组化方法对上述患者癌组织中的雌激素受体(ER)α、ERβ及孕激素受体(PR)表达进行测定;采用放射免疫或酶联免疫吸附试验方法对上述患者血清转化生长因子α(TGFα)和降钙素水平进行测定.同时采用欧洲癌症研究与治疗组织的生命质量核心量表和自制的特异性量表对上述患者和健康绝经对照妇女进行问卷调查.结果 (1)HT组和非HT组患者的平均生存时间分别为(1108±52)、(1086±43)d,两组比较,差异无统计学意义(P=0.940).经Cox比例风险模型分析,HT不是影响预后的独立因素.(2)HT组和非HT组癌组织中ERα、ERβ及PR不同表达状况患者的累积生存期比较,差异均无统计学意义(P>0.05).(3)手术前、手术后20 d、手术后半年至1年,HT组患者的血清TGFα水平分别为(30±23)、(13±7)、(13±10)ng/L,与非HT组分别比较,差异均无统计学意义(P>0.05).(4)非HT组患者在手术后半年至1年的血清降钙素水平明显高于HT组患者[分别为(141±13)、(90±18)μg/L],两组比较,差异有统计学意义(P<0.05);而HT组患者与其手术前[(93±14)μg/L]比较,差异无统计学意义(P>0.05).(5)生命质量核心量表功能子量表的躯体功能、情绪功能得分及症状子量表得分,HT组分别为(1.84±1.50)、(1.45±0.82)、(6.82±2.61)分,非HT组分别为(12.69±10.20)、(12.90±11.61)、(21.82±10.85)分,两组分别比较,差异均有统计学意义(P<0.05).在特异性量表中,HT组和非HT组患者的性生活、植物神经功能失调得分,HT组分别为(1.05±0.74)、(1.77±1.08)分,非HT组分别为(10.10±3.21)、(13.09±4.30)分,两组分别比较,差异均有统计学意义(P<0.05).结论 HT对卵巢恶性肿瘤的预后无明显不良影响.HT有助于保持血清降钙素水平的稳定并改善其生活质量,血清TGFα水平以及癌组织中ERα、ERB及PR的表达状况对HT与预后的关系无影响.     

雌激素受体β在卵巢透明细胞癌细胞增殖中的作用

目的了解导入外源性人类全长雌激素受体(ER)β cDNA 后,卵巢透明细胞癌细胞系Es-2生长情况和细胞周期的变化。方法将带有 ERβ cDNA 的质粒 pRSV-ERβ和对照空质粒 pRSV分别转染 ES-2细胞(分别命名为 ES-pRSV-ERβ、ES-pRSV 细胞),RT-PCR 和蛋白印迹法检测 ERβmRNA 和蛋白的表达情况,四甲基偶氮唑蓝法、流式细胞仪监测 ES-2、ES-pRSV、ES-pRSV-ERβ细胞在雌激素作用下的体外增殖能力、细胞周期的变化,并观察 ES-2、ES-pRSV、ES-pRSV-ERβ细胞接种于裸鼠皮下的成瘤和种植瘤的生长情况,分别将裸鼠命名为 ES-2、ES-pRSV 和 ES-pRSV-ERβ组。结果ES-pRSV-ERβ细胞稳定表达 ERβ mRNA 和蛋白,而 ES-pRSV 和未转染的 ES-2细胞均未检测出 ERβmRNA 和蛋白的表达条带。ES-pRSV-ERβ细胞在体外的增殖速度明显落后于未转染的 ES-2和 ES-pRSV 细胞,雌激素作用7d 后,未转染的 ES-2细胞的吸光度值为0.78±0.05,ES-pRSV 细胞为0.81±0.06,两者比较,差异无统计学意义(P>0.05);而 ES-pRSV-ERβ细胞的吸光度值为0.53±0.07,明显低于 ES-pRSV 和未转染的 ES-2细胞,差异有统计学意义(P<0.01)。裸鼠接种第24天,ES-pRSV-ERβ组的种植瘤平均体积为(2868±879)mm~3,低于 ES-2组的(3603±724)mm~3和 ES-pRSV 组的(3913±624)mm~3(P<0.05)。未转染的 ES-2、ES-pRSV、ES-pRSV-ERβ细胞 S 期细胞所占比例分别为(37±9)%、(39±10)%、(20±5)%,ES-pRSV-ERβ细胞分别与未转染的 ES-2、ES-pRSV 细胞比较,差异有统计学意义(P<0.05)。结论稳定表达 ERβ的 ES-2细胞体内、体外增殖能力明显减弱,ERβ以雌激素依赖方式使 ES-2细胞周期中 S 期细胞比例减少,提示 ERβ可能有肿瘤抑制作用。     

4.1N蛋白抑制人卵巢透明细胞癌细胞迁移侵袭及其机制初探

目的:探讨4.1N蛋白对卵巢透明细胞癌细胞迁移和侵袭能力的调控并初步探讨相关分子机制。方法:应用免疫组化法检测4.1N蛋白在卵巢透明细胞癌组织中的表达缺失状况。建立4.1N稳定转染卵巢透明细胞癌ES-2细胞系,通过划痕实验、Transwell迁移和侵袭实验观察细胞迁移侵袭能力的改变。利用qRT-PCR和Western blot法检测紧密连接相关分子(Claudin-4和ZO-1)、上皮-间质转化(EMT)标记物(E-cadherin、Ncadherin和Vimentin)和相关转录因子(Twist、Slug和ZEB-2)及基质金属蛋白酶(MMP-2和MMP-3)表达水平的变化。结果:与卵巢异位的子宫内膜组织相比,卵巢透明细胞癌中4.1N蛋白表达水平显著降低甚至缺失(P0.0001)。过表达4.1N后,ES-2细胞的迁移和侵袭能力显著降低,Claudin-4和ZO-1表达上调,Twist、Slug、ZEB-2、MMP-2和MMP-3表达水平下降。结论:4.1N在卵巢透明细胞癌细胞中可能通过调控紧密连接蛋白、部分上皮-间质转化转录因子和基质金属蛋白酶的表达水平,抑制癌细胞的迁移和侵袭能力,进而参与负性调控卵巢透明细胞癌的演进。     

Ruptured ovarian granulosa cell tumors as a cause of the acute abdomen

A rare case of acute abdomen syndrome due to a ruptured ovarian tumor and a penetrated fallopian tube is described. Based on the intraoperative finding and patient’s age, a right-sided salpingo-oophorectomy, appendectomy and peritoneal washings were performed. After a histological diagnosis of malignant granulosa cell tumors and FIGO IIA clinical classification, the patient returned 1 month after the procedure. A relaparotomy with a hysterectomy, left-sided salpingo-oophorectomy and omentectomy were then performed. No spread was found during the laparotomy, and the histologic diagnosis pointed to adenomyosis and chronic cervicitis. The patient regularly presents for control examination, and has now been free for 11 years since the surgery from clinical, biochemical or ultrasonographic signs of a relapse of the disease. Received: 3 August 2001 / Accepted: 8 October 2001 Correspondence to D. Habek     

Clear cell adenocarcinoma of the endometrium is a biologically distinct entity from endometrioid adenocarcinoma

Clear cell adenocarcinoma (CCA) of the endometrium has a poor prognosis, although the biologic features of this rare tumor are not clear. In this study, we analyzed the expression of biologic markers relating to carcinogenesis, tumor growth, and progression. Thirteen cases of CCA were compared with cases of endometrioid adenocarcinoma (EMA) of the endometrium. Immunohistochemical staining for p53; Ki-67; cyclins A, D1, and E; E-cadherin; progesterone receptor (PR)-A and PR-B; P-glycoprotein; MLH1; and MSH2 was performed. Labeling indices of p53, Ki-67, and cyclins A, D1, and E in CCA were 46.4 +/- 24.3%, 52.1 +/- 20.5%, 37.9 +/- 21.4%, 12.3 +/- 27.9%, and 8.2 +/- 22.9%, respectively. E-cadherin was expressed in only 1 case (7.7%) of CCA, as compared to 39 cases (61.0%) of EMA. No CCAs were positive for PR-A and PR-B. P-glycoprotein was detected in seven cases (53.8%). Loss of either MLH1 or MSH2 expression occurred in eight cases (61.5%). High-level expression of p53, cyclin A, and P-glycoprotein, and low-level or no expression of cyclin E, E-cadherin, PR-A, and PR-B was observed in CCA compared with EMA. The mechanism of cell-cycle regulation in endometrial CCA is different from that in EMA and may influence its malignant potential. Endometrial CCA is a distinct entity from EMA.     

Concurrent primaries of vaginal clear cell adenocarcinoma and endometrial adenocarcinoma in a 39-year old woman with in utero diethylstilbestrol exposure

Abstract. Keller C, Nanda R, Shannon RL, Amit A, Kaplan AL. Concurrent primaries of vaginal clear cell adenocarcinoma and endometrial adenocarcinoma in a 39-year-old woman with in utero diethylstibestrol exposure.
Diethylstilbestrol (DES) was used widely in the late 1940s in an attempt to prevent adverse pregnancy outcomes. In 1971 the US Food and Drug Administration proscribed its use for pregnancy support secondary to its association with clear cell adenocarcinoma of the vagina. Several studies in animal models demonstrated an association with endometrial cancer among offspring following in utero DES exposure. To date, there is only one case report of endometrial cancer in women exposed to DES in utero . We present the first case, to our knowledge, of a woman exposed to DES in utero who presented with double primaries of clear cell cancer of the vagina concomitant with endometrial cancer.