Amylase-producing ovarian cancer treated with postoperative QF chemotherapy--a case report

A case of an amylase-producing ovarian cancer in 69-year-old woman has been investigated by light and electron microscopy, as well as by amylase isozyme analysis. Serum and urinary amylase levels were found to be elevated, especially by an amylase isozyme analysis of the tumor homogenate which revealed a salivary type of cancer. The serum amylase level and its isozyme pattern returned to normal following therapy. Pathological examination revealed a serous cystadenocarcinoma. The ultrastructure of this tumor resembled that of other ovarian serous cystadenocarcinomas. No zymogen granules were recognized. Thus, a biochemical analysis of amylase isozyme was found to be a useful tumor marker for diagnosis and treatment of an amylase-producing ovarian serous neoplasm.     

Amylase-producing ovarian neoplasm with pseudo-Meigs' syndrome and elevated pleural fluid amylase: case report and ultrastructure.

Elevated amylase activity was noted in the pleural effusion of a patient who was later found to have a stage I low-grade serous papillary ovarian neoplasm. The effusion resolved spontaneously after resection of the ovarian tumor, which contained large amounts of amylase activity. The ultrastructure of the tumor epithelium resembled that of normal salpinx. Secretory-type cells were present with apical, variably electron-dense secretory granules and cytoplasmic glycogen deposits. Amylase activity in the ovarian neoplasm probably resulted from the presence of functioning endosalpingeal-type epithelium in the tumor. In cases of effusion with unexplained amylase elevations, the possibility of serous ovarian neoplasia should be considered, even in the absence of demonstrable extra-ovarian dissemination.     

血清中人附睾蛋白4、抑制素A及癌胚抗原125联合检测在卵巢癌诊断中的意义

目的：探讨人附睾蛋白4（HE4）、抑制素A（inhibinA）及癌胚抗原125（CA125）在卵巢癌患者中的诊断价值。方法：应用ELISA法检测卵巢癌组、卵巢良性肿瘤组及正常对照组患者血清中HE4、InhibinA、CA125水平。结果：血清HE4水平：卵巢癌组（133.86±127.94）pmol/L、卵巢良性肿瘤组（42.67±22.77）pmol/L、正常对照组（33.40±19.50）pmol/L;血清InhibinA水平：卵巢癌组（177.22±114.35）ng/L、卵巢良性肿瘤组（76.60±14.10）ng/L、正常对照组（70.70±21.66）ng/L;血清CA125水平：卵巢癌组（750.52±1230.34）U/L、卵巢良性肿瘤组（67.25±106.16）U/L、正常对照组（17.69±6.13）U/L。统计学分析血清HE4、InhibinA数值显示：卵巢癌组与卵巢良性肿瘤组、正常对照组比较,P〈0.05,差异有统计学意义;而卵巢良性肿瘤组与正常对照组比较,P〉0.05,差异无统计学意义。血清CA125卵巢癌组与卵巢良性肿瘤组、正常对照组比较,P〈0.05,差异有统计学意义;良性肿瘤组与正常对照组比较,P〈0.05,差异有统计学意义。卵巢癌诊断中的阳性率分别是：HE4 71.8%、InhibinA 66.7%、CA125 61.5%,三者联合阳性率为92.3%。结论：HE4、InhibinA、CA125在卵巢癌诊断中有重要意义,三者联合检测能明显提高卵巢癌的诊断率。     

Ovarian serous adenocarcinoma with functioning stroma and production of estrogen and alpha-fetoprotein

A 60-year-old woman with a left ovarian tumor had a high level of serum estrogen and alpha-fetoprotein (AFP). Serum estrogen levels decreased to the normal level shortly after the operation. The resected tumor presented marked luteinization of stromal cells, and immunohistochemically, AFP was found to be positive in some tumor cells.     

An amylase-producing serous cystadenocarcinoma of the ovary

A patient with an amylase-producing serous cystadenocarcinoma of the ovary had elevated serum and urine amylase levels and high levels of amylase in pleural and ascitic fluids. Serum and urine amylase levels reflected both surgical removal of tumor mass and response to chemotherapy. Tumor homogenates had pronounced amylase activity. Salivary type amylase isozyme patterns were found in electrophoresis of samples from all sources. Ascites tumor cells were successfully cultured and salivary type amylase was found in the culture media throughout 5 passages. The tumor was classified by light microscopy as poorly differentiated serous cystadenocarcinoma. Ultrastructural studies on the tumor were consistent with that diagnosis. Amylase was detected in the cells of the tumor examined by the immunoperoxidase technique.     

The modified radioimmunoassay of serum inhibin and its value in monitoring ovarian tumor

Inhibin(INH)isakindofpolypeptideglycoproteinhormone'secretedfromovariangranulosacells.It'schiefphysiologicaleffectistoinhibitproductionandsecretionoffolliclestimulatinghormone(FSH)byanteriorpituitarygland.Therehavebeensomereports"-"whichsuggestedthatthedeterminationofserumINHcontentswouldbevaluableformonitoringovariancancer,trophoblasticdiseaseandDown'ssyndrome.Tomakeawidespreadapplicationinclinic,aconvenient,sensitive,andaccuratemethodisneededformonitoringserumINHlevels.Inthisstudy,wees…     

血清前白蛋白作为上皮性卵巢癌生物学瘤标的初步研究

目的了解上皮性卵巢癌患者血清前白蛋白（ｐｒｅａｌｂｕｍｉｎ,简称ＰＡ）水平与上皮性卵巢癌肿瘤生物学行为的关系及其作为上皮性卵巢癌生物学瘤标的意义。方法采用琼脂糖免疫单向扩散法测定５８例上皮性卵巢癌、３５例上皮性卵巢瘤和３０例正常人血清前白蛋白。同时用放免法测定上述检测对象血清ＣＡ１２５。结果上皮性卵巢癌组血清ＰＡ低于上皮性卵巢瘤组及正常人组（Ｐ＝０．００３）。且肿瘤临床分期越晚、分化越差,ＰＡ水平越低（Ｐ＜０．００１;Ｐ＝０．０２７）,有淋巴转移者血清ＰＡ较无淋巴转移者低（Ｐ＜０．００１）;术后肿瘤残存与血清ＰＡ低水平有关（Ｐ＝０．０１４）。ＰＡ与ＣＡ１２５呈负相关,Ｓｐｅａｒｍａｎ′ｓ系数为—０．６８（Ｐ＜０．０１）,ＰＡ越低ＣＡ１２５越高,与上皮性卵巢癌恶性生物学行为一致。结论ＰＡ与上皮性卵巢癌恶性行为密切相关,可作为上皮性卵巢癌病情及预后估计较敏感的新指标。     

Gonadotropin, steroid, and thyroid hormone milieu of young SWR mice bearing spontaneous granulosa cell tumors

Young SWR mice possessing spontaneous ovarian granulosa cell (GC) tumors were examined for evidence of endocrine dysfunction associated with tumorigenesis. Tissue levels of hormones in tumor host and normal control females were measured by radioimmunoassays, ovarian luteinizing hormone (LH) receptors by uptake of 125I-labeled human chorionic gonadotropin (hCG) administered iv, and ovarian 3-beta-hydroxysteroid dehydrogenase (3-beta-OH) activity by histochemical techniques. When data from tumor host mice were compared with control data, hypothalamic gonadotropin releasing hormone content was not significantly different. Pituitary LH and follicle-stimulating hormone (FSH) contents were significantly decreased. Serum FSH, but not LH, levels were significantly reduced. No specific uptake of 125I-labeled hCG by tumor tissue was detected, whereas uptake by nontumorous contralateral ovaries was identified and found to be similar to that of control ovaries. With respect to serum steroids in tumor host mice, progesterone, dihydrotestosterone, and testosterone were significantly reduced, whereas androstenedione, dehydroepiandrosterone, corticosterone, estrone, and estradiol were normal. Frozen sections of tumor tissue failed to show any 3-beta-OH activity, whereas prominent activity was observed in non-tumorous contralateral and control ovaries. Serum thyroxine levels, evaluated because of the known depressive effects of hypothyroidism on reproductive function, were found to be significantly elevated in tumor host mice. The above results suggest that in SWR mice with spontaneous GC tumors, gonadotropins are moderately suppressed; the granulosa tumor cells do not have LH-hCG receptors; steroidogenesis by tumor tissue is reduced, whereas peripheral conversion of adrenal androgen precursors to estrogens is normal; and elevated serum thyroxine levels have a secondary role in established GC tumors.     

Evaluation of 5'-nucleotidase as an enzyme marker in ovarian carcinoma

A plasma membrane ectoenzyme in mammalian cells, 5'-nucleotidase, was evaluated as a marker for ovarian carcinoma. Activities of this enzyme were determined in homogenates from normal (N = 17) and malignant ovaries (N = 17), as well as in the sera from control women (N = 35), ovarian cancer patients with active disease (N = 24), and those in clinical remission (N = 9). A significant reduction of the activity of 5'-nucleotidase was observed in tumor homogenates compared with homogenates from normal ovaries. Levels of this enzyme in the sera of ovarian cancer patients were higher than in control women, suggesting the possibility of shedding of this enzyme from the tumor cell surface to the systemic circulation of the host. The diagnostic value of serum 5'-necleotidase levels was compared with another enzyme marker for ovarian carcinoma, viz. serum glycoprotein:galactosyltransferase. The upper limit of normal was set at 2 SD higher than the normal mean. Elevation of serum 5'-nucleotidase was observed in 12/24 (50%) patients with active disease, and 1/9 (11%) patients with clinical remission. In contrast, serum glycoprotein:galactosyltransferase was elevated in all the serum samples from patients with active disease and in none of those with clinical remission. There was some correlation between the serum levels of 5'-nucleotidase and those of glycoprotein:galactosyltransferase (0.01 less than P less than 0.05). Elevation of 5'-nucleotidase in the serum of these patients was not due to liver metastasis. Serum 5'-nucleotidase levels seem to correlate with disease status in some ovarian carcinoma patients, but in general it is inferior to serum glycoprotein:galactosyltransferase as a tumor marker.     

检测卵巢上皮性肿瘤患者血清和肿瘤组织中VEGF的临床意义

背景及目的:本研究拟通过对卵巢上皮性肿瘤患者血清血管内皮生长因子(vascularepithelialgrowthfactor,VEGF)水平的检测及对卵巢上皮性肿瘤组织中VEGF表达的观察,以探讨VEGF与卵巢上皮性肿瘤临床、病理诸因素的关系。方法:卵巢上皮性肿瘤患者73例,其中24例为良性肿瘤患者(良性组),7例为交界性上皮瘤患者(交界性组),42例为恶性肿瘤患者(恶性组);以同期在本科室查体无明显妇科疾患的20名妇女血清做对照。用免疫组化二步法检测73例卵巢上皮性肿瘤患者肿瘤组织中VEGF的表达,用ELISA法测定71例卵巢上皮性肿瘤患者术前血清及10例患者腹水中VEGF水平,对其中7例卵巢上皮性癌患者血清在术后进行了定期检测。结果:①VEGF在卵巢上皮性肿瘤组织中的表达,恶性组阳性表达率(86.36%)明显高于交界性组(66.67%,P<0.005)及良性组(37.50%,P<0.005)。②良性组、交界性组及恶性组之间血清VEGF水平的差异有统计学意义(P<0.01);在恶性组中,血清VEGF水平在临床Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期(P<0.05),在病理分化差的G3组明显高于病理分化好的G1、G2组(P<0.01),而与病理类型相关性无统计学意义;卵巢癌患者经理想的肿瘤细胞减灭术后,血清VEGF水平均有不同程度下降,有3例患者病情复发后,血清VEGF水平再度上升。结论:①VEGF在卵巢上皮性肿     

Serum amylase is a sensitive tumor marker for amylase-producing small cell lung cancer?

A 68-year-old male smoker was diagnosed as having amylase-producing small-cell lung cancer (SCLC). The serum amylase level was elevated, at 1756 IU/l, and the isozyme pattern was salivary type. Serum levels of “the tumor markers” CEA and NSE were 10.0 ng/ml and 22.6 ng/ml, respectively, but the level of pro-GRP was within the normal range. He was treated with combination chemotherapy of carboplatin and irinotecan. After completion of the chemotherapy, the serum amylase level decreased below the cutoff range and a computed tomography (CT) scan of the chest revealed marked reductions of the tumor in the primary site and in the lymph node metastasis. In November 2003, he was noted to have a slightly raised amylase level, of 168 IU/l, and raised levels of tumor markers. At this time, a CT scan, bone scintigraphy, and magnetic resonance imaging (MRI) of the brain demonstrated no recurrence. However, in December, MRI of the brain showed multiple metastases, and the recurrence of SCLC was thus confirmed. For the treatment of disease progression, the same regimen of chemotherapy as that given initially was administered. CT imaging revealed a partial response in the primary site and lymph node metastasis, and the serum amylase level decreased to 91 IU/l. After the completion of the second chemotherapy regimen, he underwent cranial irradiation and further chemotherapy. However, unfortunately, he died owing to deterioration of lung cancer. In this patient, the serum amylase level was found to be a highly sensitive marker of lung cancer.     

Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary.

Serum AFP was determined serially by radioimmunoassay in 13 patients with ovarian germ cell tumors and in one patient with bilateral pure gonadoblastoma. There were 4 patients with pure dysgerminoma, one with pure endodermal sinus tumor (EST) and 8 with mixed germ cell tumors, all containing EST. The patients with dysgerminoma and gonadoblastoma had normal serum AFP at all times. All patients with tumors containing EST had raised serum AFP, although in most cases it was first determined between 1 and 3 weeks after operation and there was no evidence of metastases. Serum AFP became normal 5 to 7 weeks after operation and began to rise when disease recurred. Serum AFP determinations detected presence of recurrent disease long before it became detectable by other methods. Serum CEA was determined serially by radioimmunoassay in 8 of these patients, including 2 who dies with metastases, and was normal on all occasions.     

转录因子NR4A2在卵巢上皮性肿瘤组织中的表达及其临床意义

目的:探讨转录因子NR4A2在卵巢上皮性肿瘤组织中的表达及其临床意义。方法:采用免疫组化SP法检测39例卵巢上皮性癌、28例交界性卵巢上皮性肿瘤、27例良性卵巢上皮性肿瘤及17例正常卵巢组织中NR4A2蛋白的表达,分析其与临床病例参数的关系。结果:NR4A2蛋白在卵巢上皮性癌、交界性卵巢上皮性肿瘤、良性卵巢上皮性肿瘤及正常卵巢组织中的阳性表达率分别为53.8%(21/39)、25.0%(7/28)、7.4%（2/27）、5.9%（1/17）。NR4A2蛋白在卵巢上皮性癌组织中的阳性表达率明显高于交界性卵巢上皮性肿瘤组织、良性卵巢上皮性肿瘤组织和正常卵巢组织（P均<0.05）。交界性卵巢上皮性肿瘤的阳性表达率虽然高于良性卵巢上皮性肿瘤及正常卵巢,但差异无统计学意义（P＞0.05）。良性卵巢上皮性肿瘤的阳性表达率高于正常卵巢组,但两组之间的阳性表达率差异无统计学意义（P＞0.05）。在卵巢上皮性癌组织中,NR4A2蛋白的阳性表达率随手术分期的增加而增加（P＜0.05）,但与病理分级以及有无淋巴结转移和来源无关（P＞0.05）。结论:在卵巢上皮性癌中转录因子NR4A2呈现明显高表达,且其表达水平与手术分期相关,提示NR4A2可能与卵巢癌的发生发展相关。     

Amylase-producing lung cancer: case report and review of the literature

A case of hyperamylasemia with lung cancer is described. Macroamylasemia was excluded by a normal amylase/creatinine clearance ratio and by a sedimentation constant obtained by sucrose density gradient centrifugation. Positive immunofluorescent staining of tumor cells with a specific antibody against human salivary amylase and significant amylase activity in the primary tumor and metastases support the hypothesis of independent production of amylase by the lung tumor. Cellulose--acetate membrane electrophoresis demonstrated three bands of amylase activity. The major component corresponded to normal salivary amylase in electrophoretic mobility, isoelectric point and molecular size. The minor bands, one of which occupied about 10% of the total amylase activity in serum, urine and tissue homogenates, demonstrated a lower electrophoretic mobility and a more acidic isoelectric point. Gel filtration and electrophoresis disclosed that these minor bands were derived from an amylase isozyme with a larger molecular size than that of normal salivary amylase. The results suggest ectopic tumor production of heterogenous amylase isozymes, with the larger form being secreted into the circulation.     

Human placental alkaline phosphatase in benign and malignant ovarian neoplasia

In benign and malignant ovarian tumor patients, human placental alkaline phosphatase (HPLAP) was determined in serum and extracts from surgical tumor biopsies using a highly specific enzyme-antigen immunoassay based on a mouse monoclonal antibody (E6) to HPLAP. Serum HPLAP levels greater than or equal to 0.1 unit/liter were found in 58% of ovarian cancer patients. Serum carcinoembryonic antigen levels were positive (greater than 5.4 ng/ml) in 17% of these patients. HPLAP was detected in extracts from 13 of the 14 tumors investigated (range, 2.4 to 557 milliunits/g). Only the mixed heterologous Müllerian sarcoma was negative. The highest HPLAP content of normal ovarian tissue was 1.1 milliunits/g. The amount of heat-stable and L-p-bromotetramisole-insensitive alkaline phosphatase was in all cases much higher than the fraction recognized by E6. The neoplastic origin of HPLAP was confirmed immunohistochemically on paraffin sections by an indirect avidin-biotin-peroxidase staining procedure using E6. The staining pattern was compared to the histochemical distribution of total alkaline phosphatase on adjacent sections. A consistency was found between the amount of HPLAP in tissue extracts and its immunohistochemical distribution. In all the tumors, staining for HPLAP was observed mainly on the plasma membranes of carcinoma cells. In 9 of the 10 carcinomas, the histological distribution of HPLAP and also of total alkaline phosphatase was heterogeneous. HPLAP staining, present in one of five normal ovaries, was restricted to germinal inclusion cysts. The present results support the hypothesis that serous ovarian tumors originate from these cysts.     

Carcinoembryonic antigen (CEA), serum amylase and pancreozymin-secretin test in relation to stages of pancreatic cancer

In cases of surgically proved pancreatic carcinoma, preoperative values of serum CEA, serum amylase and pancreozymin-secretin test (PST) were seen if they related to the macroscopic stages of the tumor determined by "General Rules for Surgical and Pathological Studies on Cancer of Pancreas" offered by Japanese Pancreatic Society in April 1982. Serum CEA was determined in 43 cases, serum amylase in 34 cases and PST was done in 28 cases. All of CEA, amylase and PST showed no statistically significant relationship to the stages of the carcinoma. This may suggest that these tests may not be a useful indicator of the stage of tumor.     

A case of advanced ovarian clear cell adenocarcinoma responding to cisplatin-cyclophosphamide and paclitaxel-carboplatin]

We report a case of stage IV ovarian clear cell adenocarcinoma successfully controlled by a combination of cisplatin-cyclophosphamide (CP) and paclitaxel-carboplatin (TJ). A 64-year-old female with advanced ovarian cancer and pleural effusion underwent 4 courses of combination chemotherapy with CP. The giant ovarian tumor showed a relative reduction in size and the pleural effusion disappeared. Serum CA-125 levels and CA 19-9 levels markedly decreased. Thus, the patient underwent a total hysterectomy and bilateral salphingoophorectomy. During the operation, a giant ovarian clear cell adenocarcinoma was found, but there was no peritoneal dissemination and no cancer cells in her peritoneal fluid. Thereafter, she underwent 3 courses of combination chemotherapy with TJ. She has had 13 months of stable, tumor-free survival since the operation and normal serum CA-125 and CA 19-9 levels. Ovarian clear cell adenocarcinoma generally responds poorly to cisplatin and carboplatin, but in combination chemotherapy with paclitaxel-carboplatin these may be effective.     

β-淀粉样蛋白在卵巢癌组织中的表达及与临床关系研究

目的 研究β-淀粉样蛋白(Amyloid beta A4 protein,APP)mRNA在卵巢肿瘤患者组织中的表达,并探讨其临床意义.方法 Trizol一步法提取卵巢肿瘤患者卵巢组织总RNA,实时荧光定量PCR技术对49例卵巢癌、20例卵巢良性肿瘤、16例正常卵巢组织进行定量分析.结果 APP mRNA在卵巢癌中表达量比在卵巢良性肿瘤和正常卵巢组织中明显升高(P＜0.05);卵巢颗粒细胞瘤患者组织APP的表达显著高于上皮性卵巢癌(P＜0.05);术前行新辅助化疗的卵巢癌患者APP表达量显著高于良性组和正常对照组,但与非化疗患者的表达没有差异,提示化疗不会降低其表达量.APP表达量与卵巢癌患者的生存率无显著相关性,不是独立判断卵巢恶性肿瘤患者预后的因素.结论 卵巢癌患者肿瘤组织APP mRNA水平显著高于良性和正常对照组,并在卵巢颗粒细胞瘤中高表达,提示其增高与恶性肿瘤的组织学类型有关,具有一定的临床诊断意义和价值.     

基于iTRAQ标记结合2D nano HPLC-ESI-OrbiTrap MS/MS技术筛选卵巢癌血清标记物

  目的  利用相对和绝对同位素标记（iTRAQ）和纳升级两维高效液相色谱-电喷雾-OrbiTrap质谱（2D nano HPLC-ESI-OrbiTrap MS/MS）蛋白组学方法探寻卵巢癌血清标记物,以提高早期卵巢癌诊断率。  方法  收集卵巢癌患者血清20例（卵巢癌组）,CA125异常的卵巢良性囊肿16例（良性囊肿组）,健康者20例（正常对照组）,每组取10例组内等量混合后去除高丰度蛋白,iTRAQ试剂标记,进行强离子交换柱分离多肽、nanoLC分离并在线连接电喷雾串联OrbiTrap质谱分析,筛选出重要的差异蛋白。随后采用Western blot方法,将筛选出的重要差异蛋白进行56例临床血清样本逐例验证。  结果  共鉴定出差异蛋白326个。其中重点筛选出了8个重要的差异蛋白:蛋白PARD3、SRP1-alpha、LAMA4、LRP16、IgSF2、NRAMP1、NF-E2-related factor 1和APOA4;验证了3个重要差异蛋白:PARD3、NRAMP1、APOA4。  结论  应用iTRAQ标记的定量蛋白质组学技术筛选出了8个重要的差异蛋白,可能是潜在的肿瘤标记物。其中APOA4蛋白有可能成为区分恶性与良性卵巢疾病的生物标志物。      

Diagnostic Performance of Serum Human Epididymis Protein 4 (HE4) for Prediction of Malignancy in Ovarian Masses

Background: Early diagnosis of ovarian cancer is essential for long term disease control and mortality reduction.This has been achieved using tumor markers like cancer antigen 125 (CA-125) which is elevated in malignant as wellas non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum humanepididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancersand comparing it with CA-125. Methods: Serum samples from 67 patients with ovarian cancer, 42 with benignovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses wascalculated and compared to each other. Results: Mean CA-125 and HE4 levels were significantly higher in patientswith ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levelssignificantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Usingbenign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off valuefor diagnosing malignancy for serum HE4 and CA-125. Compared to CA-125, HE4 had a similar sensitivity (83.6%vs. 85.10%) and higher specificity (100% vs. 90.48%); combination of serum HE4 and CA-125 improved the sensitivityto detect ovarian cancer to 92.54%. Sensitivity of HE4 to detect early stage ovarian cancer was superior to CA-125(92.61% vs. 63.41%). Conclusion: Serum HE4, a novel tumor marker, discriminated epithelial ovarian cancer frombenign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinousepithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may providehigher accuracy for detecting epithelial ovarian cancer particularly in the early stages.