Differences of chemoresistance assay between invasive micropapillary/low-grade serous ovarian carcinoma and high-grade serous ovarian carcinoma

The objective of this study was to evaluate the pattern of chemoresistance in invasive micropapillary/low-grade serous ovarian carcinoma (invasive MPSC/LGSC) and high-grade serous ovarian carcinoma (HGSC) according to extreme drug resistance (EDR) assay testing. Surgical specimens of 44 recurrent ovarian cancer patients harvested at the time of cytoreductive surgery between August 1999 and February 2004 were identified retrospectively from the tumor registry database. Thirteen patients (29.5%) had recurrent invasive MPSC/LGSC and 31 (70.5%) patients had recurrent HGSC. Eight drugs were evaluated; EDR assay results were compared between LGSC and HGSC groups using Fisher exact tests and exact logistic regression models. Compared to HGSC, invasive MPSC/LGSC were more likely to manifest EDR to the drugs paclitaxel (69% vs 14%, P < 0.001), carboplatin (50% vs 17%, P= 0.05), cyclophosphamide (40% vs 23%, P= 0.41), gemcitabine (36% vs 19%, P= 0.40), and cisplatin (33% vs 28%, P= 0.72) and less likely to be resistant to etoposide (0% vs 44%, P= 0.007), doxorubicin (8% vs 45%, P= 0.03), and topotecan (8% vs 21%, P= 0.65). Exact logistic regression estimates revealed that invasive MPSC/LGSC patients had significantly increased probabilities of paclitaxel resistance odds ratio (OR) = 12.5 (95% CI: 2.3-100.0), P= 0.001 and carboplatin resistance OR = 4.8 (95% CI: 0.9-25.0), P= 0.07, while the HGSC cases were more likely to be resistant to etoposide OR = 12.1 (95% CI: 1.7-infinity), P=0.009 and doxorubicin OR = 8.6 (95% CI: 1.0-413.7), P= 0.05. In this retrospective analysis, patients with recurrent invasive MPSC/LGSC were more likely to manifest EDR to standard chemotherapy agents (platinum and paclitaxel). These observations may help to guide chemotherapeutic decision making in these patients if confirmed in a large-scale study.     

Concurrent ovarian serous carcinoma and osteogenesis imperfecta

Summary Because epithelial malignancies in patients with osteogenesis imperfecta are rare, it has been postulated that these patients may have “cancer-protection”. A case of stage III b ovarian serous carcinoma in a woman with congenital osteogenesis imperfecta is now presented and discussed.     

Pretreatment maximum standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography-computed tomography as a prognostic factor for ovarian clear cell carcinoma and low-grade serous carcinoma

ObjectiveThe maximum standardized uptake value (SUVmax) derived by positron emission tomography-computed tomography (PET/CT) can be an index of biological tumor aggressiveness, which is assessed using noninvasive tools before the treatment of epithelial ovarian cancer (EOC). This study aimed to evaluate the prognostic value of the pretreatment SUVmax in patients with EOC.Materials and methodsWe reviewed the data of patients with EOC who underwent pretreatment 18F-FDG PET/CT between June 2006 and September 2016. The relationships between pretreatment SUVmax and histological subtypes of EOC were determined. Moreover, progression-free survival (PFS) and overall survival (OS) were evaluated according to the pretreatment SUVmax. Risk factors associated with progression or death were also analyzed.ResultsOf 148 patients, 66 (44.6%), 11 (7.4%), 34 (23.0%), 19 (12.8%), 15 (10.1%), and three (2.0%) were diagnosed with high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell carcinoma (CCC), endometrioid carcinoma, mucinous carcinoma, and others, respectively. The median SUVmax was marginally lower in LGSC (6.80 vs. 10.5; P = 0.059) and significantly lower in CCC (5.92 vs. 10.5; P = 0.001) than in HGSC. A high pretreatment SUVmax (≥9.30) was a prognostic factor for OS in patients with LGSC (P = 0.046). Furthermore, multivariate analysis revealed that a high SUVmax (≥5.85) was an independent prognostic factor for OS (P = 0.046) in patients with CCC. However, a high SUVmax (≥7.77) was a poor predictor of PFS and OS in patients with EOC (P = 0.156 and P = 0.158, respectively).ConclusionOur findings suggest that the pretreatment SUVmax is not only an independent predictor of survival in patients with CCC but also a significant predictor of survival in patients with LGSC.     

"Primary peritoneal" high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer

Objective

Primary peritoneal high-grade serous carcinoma is thought to arise from the peritoneum, but recent data suggest that the fallopian tube may be an occult source of many of these tumors. This study was performed to evaluate this hypothesis in an unselected series of cases.

Methods

Fallopian tubes from 51 consecutive cases meeting the GOG criteria for primary peritoneal high-grade serous carcinoma, FIGO stages II-IV, were analyzed.

Results

Serous tubal intraepithelial carcinoma (STIC) was identified in 19 patients (37%). When the fimbriae were examined, STIC was identified in 46%, and when all tubal tissue was examined, 56%. STIC was confined to the fimbriae in 53%, involved fimbriae and nonfimbrial mucosa in 20%, and was confined to nonfimbrial mucosa in 20%. Patients with STIC were significantly older than those without STIC (75 years vs. 67 years, respectively; p = 0.007). Patients with STIC were significantly more likely to have FIGO stage IV disease as compared to those without STIC (42% vs. 12.5%, respectively; p = 0.037).

Conclusions

At least half the cases of primary peritoneal high-grade serous carcinoma are associated with intraepithelial carcinoma of the fallopian tube, usually involving the fimbriae. These findings support the view that, like “primary ovarian carcinoma,” what has been traditionally classified as “primary peritoneal carcinoma” is probably derived from occult high-grade serous carcinoma in the fallopian tube. These findings have important implications for ultrasound screening trials for ovarian cancer which are based on the assumption that an enlarged ovary is a very early manifestation of disease.     

Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: implications for ovarian cancer screening

OBJECTIVE: Our purpose was to report the cancers arising during a familial ovarian cancer screening program and investigate the tumor's clonality and association with BRCA1 and BRCA2 mutations. STUDY DESIGN: Program participants with a diagnosis of ovarian cancer or peritoneal serous papillary carcinoma were identified and their demographic characteristics, ultrasonographic findings, CA 125 results, operative reports, and pathology slides reviewed. Immunohistochemical analysis of p53, bcl-2, HER-2/neu, and nm23 H1 expression was performed on tumor tissues from multiple metastatic sites, and germline BRCA1 and BRCA2 mutations were identified. RESULTS: Three stage I ovarian cancers and 7 cases of peritoneal serous papillary carcinoma were diagnosed from among 1261 program participants. Ultrasonographic abnormalities triggered surgical exploration in all 3 cases of stage I disease. Elevated levels of CA 125 were the harbinger in 2 of 7 cases of peritoneal serous papillary carcinoma, abnormal ultrasonographic findings prompted diagnosis in 2 of 7 cases, and 3 of 7 women had abdominal symptoms 5, 6, and 16 months after screening. Results of immunohistochemical studies suggested multifocal disease in 5 of 7 patients with peritoneal serous papillary carcinoma. At least 3 of the patients with peritoneal serous papillary carcinoma carry BRCA1 185delAG mutations. CONCLUSION: Multifocal peritoneal serous papillary carcinoma may be a phenotypic variant of familial ovarian cancer, and screening strategies for these women cannot rely on ultrasonography and CA 125 testing to detect early disease.     

卵巢浆液性腺癌预后评分模型的建立及应用

目的通过分析卵巢浆液性腺癌的预后相关因素,建立其预后评分模型,并应用于临床预测患者的生存概率。方法对北京大学人民医院104例卵巢浆液性腺癌患者的临床病理资料进行回顾性分析。Kaplan-meier单因素生存分析筛选预后相关因素;COX单因素和多因素回归分析确定各预后相关因素内分层因素及各预后相关因素的风险系数;Pearson等级相关分析剔除各预后相关因素间的相互影响。根据上述两个风险系数对各预后相关因素进行评分,建立预后评分模型,据此预测患者的生存概率。结果单因素生存分析显示,手术病理分期（P=0、0029）、病理分级（P=0．0054）、术后残留灶直径（P=0．0000）、淋巴结转移（P=0．0000）以及化疗情况（P=0．0000）是卵巢浆液性腺癌的预后相关因素。Pearson等级相关分析显示,手术病理分期对预后的影响最大,随后依次为化疗、淋巴结转移、病理分级以及术后残留灶直径（其独立风险系数分别为1．3392、0．9206、0．7071、0．6004、0．4985）。根据预后风险系数对各预后相关因素进行评分,得到了卵巢浆液性腺癌的预后评分模型。通过该模型量化了化疗和术后残留灶直径这两个可变因素对患者生存概率的影响。随着预后评分的增加,患者的生存概率降低。结论通过筛选影响预后的相关因素,建立卵巢浆液性腺癌的预后评分模型。该模型可以量化预后相关因素,尤其是化疗和残留灶直径这两个指标,预测患者的生存概率,为临床工作提供了一种科学判断预后的方法。     

卵巢浆液性癌B7-H4的表达及临床病理意义

目的:探讨B7-H4在卵巢上皮性肿瘤浆液性癌中的表达及其临床病理意义。方法:用逆转录聚合酶链反应(RT-PCR)技术及免疫组织化学染色的方法检测6例良性卵巢上皮性肿瘤、10例交界性卵巢上皮性肿瘤、41例卵巢浆液性癌、5例内膜样癌、2例透明细胞癌和10例粘液性癌标本中B7-H4 mRNA及蛋白表达,并结合临床病理资料对其中41例卵巢浆液性癌中B7-H4蛋白的表达进行分析。结果:B7-H4 mRNA在74例卵巢上皮性肿瘤中均有表达,B7-H4蛋白在良性卵巢上皮性肿瘤、交界性卵巢上皮性肿瘤、恶性卵巢上皮性肿瘤中的表达阳性比例分别为2/6、6/10、52/58,恶性标本阳性率明显高于非恶性标本,差异有统计学意义(P<0.05);58例恶性卵巢上皮性癌标本中浆液性癌、内膜样癌、透明细胞癌、黏液性癌的B7-H4蛋白阳性比例分别为41/41、5/5、2/2、4/10,前三种病理类型B7-H4蛋白阳性率明显高于最后一种,且差异有统计学意义(P<0.05);41例卵巢浆液性癌标本中B7-H4蛋白阳性细胞比例在<10%,>10%~50%,>50~80%,>80~100%4组中的分布差异无显著性(P>0.05),且其蛋白表达与临床分期及病理分级有关(P<0.05),而与患者年龄、腹水细胞学、淋巴结转移无关(P>0.05)。结论:B7-H4在卵巢浆液性癌的高表达及其与临床分级分期的关系,提示其可能与肿瘤发生发展有关,可为卵巢恶性肿瘤诊断及治疗提供靶位点。     

Expression of cellular apoptosis susceptibility protein in serous ovarian carcinoma: a clinicopathologic and immunohistochemical study

OBJECTIVE: This study investigated the expression of cellular apoptosis susceptibility protein (CAS) in serous ovarian carcinoma by immunohistochemistry and compared it with topoisomerase IIalpha (topo IIalpha), bcl-2, bcl-x, the frequency of apoptotic bodies (ABI), mitotic activity, and c-erbB-2 with regard to clinicopathologic variables. METHODS: Formalin-fixed, paraffin-embedded archival tissue sections of 10 benign serous cystadenomas, 10 serous neoplasms of low malignant potential (LMP), and 41 serous ovarian carcinomas were immunostained with antibodies to CAS, bcl-x, topo IIalpha, bcl-2, and c-erbB-2. Immunostaining for CAS, bcl-x, and bcl-2 was scored concerning approximate percentage of positive tumor cells and relative staining intensity. For c-erbB-2, at least 10% of tumor cells had to display membrane staining. Topo IIalpha-labeling indices were quantitated as the percentage of positively stained nuclei in 1000 tumor cells. ABIs were reported as the number of apoptotic bodies in 1000 tumor cells, mitotic activity as mitotic figures per 10 high power fields. RESULTS: CAS expression was negative in serous cystadenomas and LMP. In contrast, moderate or strong immunostaining was observed in 34 of 41 cases (83%) of serous carcinomas. CAS immunoreactivity was positively related with ABI (P = 0.0170), mitotic activity (P < 0.0001), c-erbB-2 (P = 0.0153), grade (P = 0.0107), and adverse outcome (P = 0.0035), but not with FIGO stage, topo IIalpha, bcl-2, and bcl-x. Other variables indicating outcome were topo IIalpha, c-erbB-2, and ABI. CONCLUSIONS: CAS is frequently upregulated in serous ovarian carcinomas, correlated with apoptosis and mitotic activity, and relevant prognostically. CAS protein expression may serve as a marker of aggressive tumor behavior in serous ovarian carcinomas.     

腹膜浆液性乳头状腺癌的临床分析

目的探讨腹膜浆液性乳头状腺癌(腹膜浆乳癌)的临床特点及治疗。方法对1984年至2002年收治的14例腹膜浆乳癌和50例卵巢浆液性乳头状腺癌(卵巢浆乳癌)患者的临床表现、治疗效果及生存率进行回顾性对比分析。结果腹膜浆乳癌患者的平均年龄为62 7岁,卵巢浆乳癌患者的平均年龄为53 6岁,两者比较,差异有统计学意义(P<0 01)。腹膜浆乳癌患者有腹水12例(86%, 12 /14),有盆腹腔包块10例(71%, 10 /14);血清CA125平均水平为2289kU/L。卵巢浆乳癌患者有腹水40例(80%, 40 /50),有盆腹腔包块45例( 90%, 45 /50 );术前血清CA125平均水平为1741kU/L。两者分别比较,差异均无统计学意义(P>0 05 )。腹膜浆乳癌患者中12例行肿瘤细胞减灭术,术后均行化疗,对化疗耐药者10例(83%, 10 /12);另2例于手术前死亡。卵巢浆乳癌50例患者均行肿瘤细胞减灭术,术后均行化疗,对化疗耐药者19例(38%, 19 /50)。两者各项比较,差异均有统计学意义(P<0 05)。腹膜浆乳癌患者1、2、3年的生存率分别为72%、10%、0;卵巢浆乳癌患者分别为95%、79%、62%。两者分别比较,差异均有统计学意义(P<0 05)。结论腹膜浆乳癌患者较卵巢浆乳癌患者的发病年龄高,化疗效果及预后差。     

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan

ObjectiveTo compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC).Materials and MethodsThis was a retrospective case–control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years).ResultsMean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum–paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3–16.7] and PSOC groups (median 16.7 months, 95% CI 12.9–20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6–104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7–85.2; p = 0.006, log-rank statistic).ConclusionPFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ.