Relationships among serum CA15-3 tumor marker, TNM staging, and estrogen and progesterone receptor expression in benign and malignant breast lesions

Serum tumor marker CA15-3 is widely used in follow-up for assessment of breast cancer prognosis. The aim of this study was to evaluate levels among healthy females and patients, to assess differences with tumor stage and grade, and to determine the relationship with estrogen and progesterone receptor expression. One hundred and thirty six Jordanian females were enrolled in this study: Forty-five were healthy females; seventy-two were diagnosed with breast cancer and nineteen diagnosed with benign breast lesions. Elevated serum CA15-3 level was significantly observed among breast cancer patients (37.95±6.65) compared to both healthy (14.97±0.8) and benign females (12.30±1.55), but no significant association was detected between serum CA15-3 level and age of cancer onset, menarche age, menopause age, parity and BMI. Decreased CA15-3 level was significantly associated with hormone therapy and oral contraceptive consumption among breast cancer patients. Significantly elevated CA15-3 serum levels were found among grade II, III and stage II and III breast cancer females compared to normal healthy females. Elevated CA15-3 serum levels were also found among ER+/PR+ (54.242±7.89) and ER+/PR- (37.08±8.22) compared to healthy control females.     

Clinical Evaluation of an Immunoradiometric Assay for CA15-3 Antigen Associated With Human Mammary Carcinomas: Comparison With Carcinoembryonic Antigen

Serum levels of CA15-3, a mammary tumor associated antigen recognizedby two different murine monoclonal antibodies (115D8 and DF3),were investigated in patients with mammary carcinoma and otherbenign or malignant diseases. The reference value of the serumCA15-3 level was obtained as 24 units/ml at the 99% confidencelimit among healthy individuals (n = 462). Elevation of serumCA15-3 levels was observed in 24.3% of overall patients withmammary carcinoma. Serum CA15-3 levels in breast cancer patientscorrelated with the clinical stage; higher percentages of positivitywere observed in those with advanced breast cancer (stage IV,64.7%, recurrent, 52.4% and metastatic, 70.3%). Furthermore,elevated serum CA15-3 levels in breast cancer patients respondedwell to the effect of therapy. Although the serum CA15-3 testgave percentages of positivity of breast cancer similar to thosefound by the serum CEA test, the serum CA15-3 test revealedlower percentages of posi-tivity than the serum CEA test amongpatients with benign breast lesions, liver cirrhosis or othercarcinomas. These results suggest that the serum CA15-3 antigenlevel provides a very useful marker for diagnosis and clinicalmonitoring of patients with breast cancer.     

TPS对转移性乳腺癌的临床应用价值

目的探讨TPS对转移性乳腺癌的临床应用价值。方法采用ELISA法测定40例健康体检者及62例乳腺癌患者(其中32例为治疗后转移复发)的血清TPS、CA15-3、CEA及TPA水平,观察11例转移性乳腺癌治疗后标志物的变化。结果TPS对转移性乳腺癌敏感性为81.3%,显著高于CA15-3及CEA(P<0.01),CA15-3对转移性乳腺癌特异性为95.5%,显著高于TPS及TPA(P<0.01),两者联合则有效性显著提高(P<0.01)。TPS对乳腺癌骨转移最为敏感,远处淋巴结转移的乳腺癌患者TPS水平最高。转移性乳腺癌治疗有效(CR+PR+SD)各标记物与治疗前相比,均无显著性变化(P>0.01),治疗无效(PD),TPS与TPA水平均显著升高,尤以TPS更甚(P<0.01)。结论TPS是检出转移性乳腺癌最为敏感的标志物,尤其是骨转移的患者。TPS与CA15-3联合是监测转移性乳腺癌的最佳组合。TPS也是与预后有关的标志物,TPS水平升高表明病情进展,预后不良。     

Plasma soluble Fas ligand concentration: decrease in elderly men and increase in patients with gastric carcinoma

Fas ligand (FasL), which induces apoptosis against Fas-expressing cells, has been found to be expressed on various cell types including cancer cells. Membrane-bound FasL is cleaved to release soluble FasL (sFasL). Although serum or plasma sFasL concentration has been reported to increase in various diseases, sFasL concentration in healthy normal persons has not been fully studied. There have been few reports on sFasL concentrations in patients with carcinomas. We measured plasma sFasL concentrations using an enzyme-linked immunosorbent assay in 155 healthy volunteers (70 males and 85 females with an average age of 41.5+/-15.4) and 112 patients with gastric carcinoma (76 males and 36 females with an average age of 62.3+/-11.5). A significant negative correlation existed between age and plasma sFasL concentration in healthy volunteers. sFasL concentrations in males were significantly lower than those in females. Plasma sFasL levels were significantly higher in patients with gastric carcinoma than in healthy volunteers when male subjects aged 50 or older were analyzed, although no significant difference existed between the groups in the age bracket of 35 to 49. Male patients aged 50 or older with stage 1B or 2 tumors showed significantly higher plasma sFasL concentrations than those with stage 1A tumors or those with stage 3 or 4 tumors. In conclusion, age- and gender-matched controls should be used when plasma sFasL concentration is investigated. The origin and physiological or clinical significance of plasma sFasL in healthy volunteers and gastric cancer patients remain to be clarified.     

Clinical usefulness of serum procollagen-III-peptide in patients with solid tumor

An attempt has been made to determine the clinical usefulness of serum procollagen-III-peptide (P-III-P) in comparison with serum CEA and AFP in patients with solid tumor. Serum P-III-P levels were measured in 82 cases of carcinoma and 64 cases of benign disease employing an AG Radiochemishes Laboratrium RIAgnost P-III-P kit. Serum P-III-P levels of 148 healthy subjects were 8.5 +/- 2.6 ng/ml (M +/- S.D.), with an upper limit of 13.7(M + 2S.D.). The serum P-III-P level in cases of hepatocellular carcinoma was elevated to 47.5 +/- 97.5 (88.9%). Serum P-III-P levels in cases of pancreatic carcinoma were elevated slightly, whereas those for patients with carcinoma of the stomach, colorectum, esophagus, and breast were low, and their P-III-P positive rates were lower than those of their serum CEA. On the other hand, the serum P-III-P levels in benign diseases involving the liver and biliary tract were higher than those in other benign diseases. Therefore, although serum P-III-P can be a useful marker in hepatocellular carcinoma, it may possibly be difficult to discriminate it from benign diseases involving the liver and biliary tract.     

Prostate-specific membrane antigen levels in sera from healthy men and patients with benign prostate hyperplasia or prostate cancer.

Prostate-specific membrane antigen (PSMA) serum levels have been proposed to be of prognostic significance in patients with advanced prostate disease. The objective of the present study was to confirm PSMA serum expression by Western blot techniques, to determine whether such data could assist in the differentiation of benign from malignant prostatic disease, and to determine the suitability of serum PSMA measurements in predicting recurrent or progressive prostate malignancies. We measured PSMA, a transmembrane glycoprotein identified in prostate epithelial cells, in the sera of 236 normal individuals and cancer patients by Western blot analysis. Within the normal male population, PSMA levels increase with age and were found to be significantly elevated in subjects more than 50 years of age when compared to those of younger men. We did not confirm previous reports that serum PSMA measurements could distinguish late-stage prostate carcinoma from early-stage prostate carcinoma, nor did we find PSMA to be more effective than prostate-specific antigen in monitoring prostate cancer patient prognosis. Furthermore, we found elevated serum PSMA in healthy females, and, similar to the healthy male population, the levels increased with age, with the highest levels found in the sera from breast cancer patients. These latter observations further support that PSMA is not a specific biomarker for prostate cancer and that a variety of normal and diseased tissue may contribute to the serum levels of PSMA.     

Measurement of prostate-specific antigen in detection of benign or malignant breast disease in women

Using a highly sensitive chemiluminescent enzyme immunoassay, we have evaluated the measurement of serum prostate-specific antigen (PSA) as a potential diagnostic test for differentiation between women with breast cancer and those with benign breast disease. In a controlled study consisting of 284 women with well-documented patient files and matched for age and long-term place of residence, serum samples collected from 90 women with histologically confirmed breast cancer, 94 women with benign breast disease and 100 controls were analysed. Serum total PSA levels in benign breast disease and cancer patients are not statistically different from those of healthy controls. Total PSA levels decrease with age in normal controls and breast cancer patients but not in those with benign breast disease. The total PSA concentration decreases after menopause in healthy women, though not in patients with breast cancer or benign breast disease. Total PSA bore no relation to the histological type or grade of the tumour or the disease stage of the breast cancer patients. In benign breast disease, all mastopathy patients had normal total PSA, whereas elevation of the values was observed in 7% of fibroadenoma patients. Our results show that serum total PSA cannot be used to distinguish between healthy women and/or women with breast cancer or benign breast disease.     

Individual and combined usefulness of lipid associated sialic acid, mucoid proteins and hexoses as tumor markers in breast carcinoma

Serum levels of lipid associated sialic acid (LASA), mucoid proteins (MP) and hexoses (galactose + mannose) were measured in 41 breast cancer patients, 14 patients with benign breast diseases and 36 healthy age matched female individuals. In breast carcinoma patients, we have observed significant increase in the levels of the three markers compared with the controls (P less than 0.001) and in MP and hexoses compared to the patients with benign breast diseases (P less than 0.001). LASA and hexoses levels were significantly higher in benign breast diseases with respect to controls (P less than 0.001 and P less than 0.01, respectively). We evaluated the sensitivity and specificity of the markers individually and in combination. MP were most sensitive (71.8%) and specific (71.4%). Both sensitivity and specificity were increased when combinations of the markers were studied. Combination of MP with LASA was most sensitive (97.4%) while the combination of MP and hexoses was most specific (92.9%). LASA was significantly elevated in infiltrating duct carcinoma compared to lobular carcinoma (P less than 0.001). MP and hexoses also showed higher mean value in infiltrating duct carcinoma than lobular carcinoma. The present study suggests that the combination of the markers investigated might be useful for diagnosis and classification of breast carcinoma.     

Study on carbohydrate antigen NCC-ST-439 in breast cancer

We evaluated the clinical significance of serum NCC-ST-439 (ST439) in sera from 20 healthy women, 8 patients with benign breast disease and 105 patients with breast cancer (79 primary, 26 recurrent) by using enzyme immuno-assay (EIA). No false positive case was noted in the measuring of ST439 for healthy women and patients with benign breast disease. The positive rates of ST439 were 23% (18/79) in primary breast cancers and 50% (13/26) in recurrent breast cancers. The serum levels of ST439 in stage I breast cancer was significantly higher (p less than 0.05) than those in healthy women, but there was no significant difference among each stage. The serum levels of ST439 were not significantly different among the subsets such as T, n, m and histological types. The high levels of serum ST439 were observed in two cases with mucinous carcinoma. Although there were no relation between ST439 and receptor status, the higher serum levels of ST439 were observed in postmenopausal patients than premenopausal ones. The positive frequency of serum ST439 in stage I and II breast cancers was higher than that of CEA, TPA or CA15-3, while the positive rate in recurrent breast cancer was the lowest among 4 tumor markers. These results suggest that ST439 is a useful tumor marker for not only detecting the recurrence of breast cancer but also diagnosing primary breast cancer in early stage.     

液相芯片分析技术检测乳腺浸润性导管癌患者血清中VEGF和MMP-9的临床意义

目的利用液相芯片分析技术检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)在乳腺浸润性导管癌(infiltrative ductal carcinoma,IDC)、良性乳腺纤维瘤患者和正常人血清中的表达,探讨其临床诊断价值。方法采用液相芯片分析技术对301例乳腺浸润性导管癌、83例乳腺良性纤维瘤患者及40例正常人血清中VEGF、MMP-9表达水平进行检测,并分析118例IDC患者手术治疗前后VEGF和MMP-9浓度变化。结果血清中VEGF和MMP-9的表达水平:乳腺浸润性导管癌患者分别为(152.76±150.28)pg/ml和(945.09±749.43)ng/ml;乳腺纤维瘤患者为(29.86±16.10)pg/ml和(563.59±183.29)ng/ml;正常人表达量为(52.45±51.39)pg/ml和(267.33±215.60)ng/ml;IDC患者显著高于乳腺纤维瘤患者和正常人(均P<0.05)。乳腺癌患者血清中VEGF、MMP-9表达水平与年龄无关(P>0.05);而与临床分期、原发灶大小及淋巴结转移相关(均P<0.01)。118例IDC患者术后复查血清VEGF、MMP-9表达量分别(135.26±131.20)pg/ml和(680.36±551.77)ng/ml,与术前相比,表达水平明显下降(均P<0.05)。结论利用液相芯片分析技术定量分析血清中VEGF和MMP-9可成为乳腺癌临床诊断和预后评估的有效指标。     

Monocyte chemoattractant protein-1 serum levels in patients with breast cancer.

The chemokine monocyte chemoattractant protein (MCP)-1 is thought to be involved in breast carcinogenesis. We evaluated MCP-1 serum levels in patients with breast cancer (n = 135), ductal carcinoma in situ (DCIS) I-III (n = 30), benign breast lesions (n = 143) and in healthy women (n = 27). We determined the value of MCP-1 serum levels as a differentiation marker between malignant, preinvasive and benign breast diseases and as a predictive marker for the biological phenotype of breast carcinoma. Median (range) MCP-1 serum levels in patients with breast cancer, DCIS I-III, benign breast lesions and healthy women were 200 (57-692) pg/ml, 194 (58-525) pg/ml, 174 (39-529) pg/ml and 175 (67-425) pg/ml, respectively. No differences were ascertained between the patient groups. In patients with breast cancer, increased MCP-1 serum levels were correlated with advanced tumor stage (p = 0.04) and lymph node involvement (p = 0.04). We were not able to establish MCP-1 as a differentiation marker between malignant and benign breast diseases. Our data might indicate that MCP-1 influences breast carcinogenesis by facilitating tumor growth and metastatic spread, thus altering the biological phenotype of the disease.     

乳腺癌患者血清可溶性肿瘤标志物的临床价值研究

目的:探讨血清可溶性肿瘤标志物CEA、CA-153、ICAM-1、E-selection单项及联合检测在乳腺癌中的诊断价值.方法:选取不同临床分期乳腺癌患者130例.乳腺良性肿瘤患者30例,正常人群30例.通过酶联免疫吸附法(ELISA)测定各项指标血清浓度并进行比较.结果:乳腺癌CEA、CA-153、ICAM-1、E-selection血清浓度均显著高于良性肿瘤组及正常人群(P<0.01),且其血清浓度与肿瘤分期密切相关.在疾病进展的转移性乳腺癌中,各指标出现明显升高(P<0.01).CEA、CA-153、ICAM-1、E-selection单项检测对于乳腺癌的诊断敏感性较低.多指标联合检测可不同程度提高检测的敏感性,以含CA-153及E-selection组合最为显著.结论:E-selection、ICAM-1、CEA、CA-153均为乳腺癌重要的血清标志物,在肿瘤的发生、发展及转移过程中发挥重要的作用.对恶性肿瘤患者的多指标联合检测可在不显著降低特异性的基础上提高诊断的敏感性,为判断预后及监测病情提供重要价值.     

不同年龄段女性血浆甘油三酯和胆固醇水平与乳腺癌的相关性分析

目的 分析不同年龄段女性血浆甘油三酯和胆固醇水平与乳腺癌的相关性.方法 选取82例女性乳腺癌患者作为实验组研究对象,另选取82例同年龄段的健康体检居民作为对照组,比较2组血浆甘油三酯和胆固醇水平;分别将实验组和研究组按照年龄段不同及体重指数不同进行分组,分别比较2组同体重指数的血浆甘油三酯和胆固醇水平.结果 实验组的血浆甘油三酯水平高于对照组,但胆固醇水平低于对照组;实验组中45岁及以上患者的血浆甘油三酯水平高于同年龄段对照组,45岁以下患者的胆固醇水平低于同年龄段的对照组;实验组中体重过轻组、正常组、肥胖组的血浆甘油三酯水平高于对照组,体重过轻组的胆固醇水平高于同体重指数的对照组,肥胖组的胆固醇水平低于同体重指数的对照组.结论 不同年龄段女性的血浆甘油三酯和胆固醇水平与乳腺癌的相关性有差异性.     

Serum CYFRA 21-1 is one of the most reliable tumor markers for breast carcinoma

BACKGROUND: The search for new tumor markers for breast carcinoma has been an area of vigorous study; nonetheless, to the authors' knowledge little new information has emerged beyond the clinical usefulness of CA 15-3. The authors studied serum CYFRA 21-1 in breast carcinoma based on evidence that breast carcinoma expresses cytokeratin 19 fragments and that CYFRA 21-1 is a specific antigen for cytokeratin 19 fragments. METHODS: The serum samples of 86 patients with primary breast carcinoma, 14 patients with recurrent breast carcinoma, 22 patients with benign mammary disease, and 25 healthy controls were provided for measurements of CYFRA 21-1, carcinoembryonic antigen (CEA), and CA 15-3. The relation between clinicopathologic features, prognosis, and disease free survival with serum CYFRA 21-1 titers was studied. RESULTS: There was no difference between the serum CYFRA 21-1 titers from patients with benign mammary disease and those from healthy controls. The sensitivities of CYFRA 21-1 for patients with International Union Against Cancer Stage IV and recurrent tumors were 60% and 64.2%, respectively, which were as high as those for CA 15-3 and superior to those for CEA. The hematogenous recurrence showed a very high sensitivity of 89%. According to the increments of T, N, and M factor numbers, the serum CYFRA 21-1 titers were elevated. No correlation between CYFRA 21-1 and CEA was observed and the correlation between CYFRA 21-1 and CA 15-3 was weak. The univariate and multivariate analyses for survival revealed that serum CYFRA 21-1 levels were an independent indicator of prognosis. CONCLUSIONS: The measurement of the serum CYFRA 21-1 titer in patients with breast carcinoma may be useful in monitoring for recurrence and evaluating the therapeutic effect in patients with advanced disease.     

c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 healthy subjects, 58 patients with benign breast diseases, and 413 patients with breast cancer (186 locoregional, 185 with advanced disease, and 42 with no evidence of disease). Using 15 U/ml as the cut-off, no healthy subjects or patients with benign diseases and only 2.4% of no evidence of disease patients had elevated serum levels. Abnormal c-erbB-2 levels were found in 29% (101/370) of the patients with breast carcinoma (locoregional 9%, metastases 45.4%). CEA (cut-off 5 U/ml) and CA 15.3 (cut-off 35 U/ml) sensitivity was 18% and 16% in patients with locoregional disease and 61% and 70% in those patients with advanced disease, respectively. A trend toward higher serum levels of all three tumor markers in patients with nodal involvement or greater tumor size was found, but was statistically significant only with CEA (p < 0.01). By contrast, c-erbB-2 was related to steroid receptors, in both locoregional and metastatic tumors. When the prognostic value of these markers was evaluated, patients with abnormally high presurgical CEA and c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative (p < 0.05 and p < 0.001, respectively) and node-positive patients (p < 0.556 and p < 0.001, respectively). By contrast, no relationship was found between CA 15.3 values and prognosis. Multivariate analysis showed that CEA and c-erbB-2 were also prognostic factors. The correlation between serum and tissue levels of c-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p=0.0001). Serum concentrations in patients with advanced disease were related to the site of recurrence, with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum levels seem to be a useful tumor marker in the prognosis of patients with breast cancer. Using all three tumor markers, sensitivity was 35% in patients with locoregional breast cancer and 88% in patients with recurrence.     

Serum lipids and tissue DNA content in Egyptian female breast cancer patients

BACKGROUND: Several clinical studies suggest the prognostic significance of serum lipid levels and tissue DNA content in breast cancer. In the course of investigating the biological features of this disease among Egyptian female patients, we examined the serum lipid levels and tissue DNA content of premenopausal and postmenopausal breast cancer patients. METHODS: Levels of total lipid, total cholesterol, and triglycerides were measured in the sera of women with breast cancer and compared with those of the control women. The DNA content in breast cancer tissue was also measured in these patients. RESULTS: Total lipid levels showed a significant increase in both premenopausal (follicular and luteal) and postmenopausal patients. Total cholesterol levels significantly increased in premenopausal (follicular and luteal) patients with no significant change in postmenopausal women. Triglyceride levels showed a significant increase in postmenopausal women, whereas no significant differences were observed in premenopausal patients. Tumors of premenopausal patients, in both follicular and luteal phases, showed a higher DNA content as compared with those of postmenopausal patients. Breast cancer tissues of grade III showed significantly higher DNA content than those of grade I and grade II. CONCLUSIONS: This study suggests an association between high levels of serum, total lipid and total cholesterol, and increased breast cancer risk in premenopausal women. Such an association is also suggested for the high total serum lipid and triglyceride levels in postmenopausal women. The DNA content in breast cancer tissue might be useful in determining a suitable therapy for individual cases, based on the malignancy grade.     

Alterations in serum glycosyltransferases and 5'-nucleotidase in breast cancer patients

We have measured sialyltransferase, galactosyltransferase, and fucosyltransferase as sell as 5'-nucleotidase in the serum of breast cancer patients. Serum sialyltransferase values in 65 normal healthy females ranged from 2.6 to 8.5 units, with a mean of 5.4. In 25 women with operable primary breast cancer, serum sialyltransferase levels were found to be between 6.2 and 15.4 units. Marked elevation of this enzyme level (range, 8.8 to 36 units) was observed in 48 patients with metastatic breast cancer. Galactosyltransferase and fucosyltransferase measurements, however, showed considerable overlap between the controls and the cancer patients. On the other hand serum 5'-nucleotidase and sialyltransferase in breast cancer patients showed very similar patterns. Thus, serum 5'-nucleotidase values in 44 normal females ranged from 11.4 to 23.2 units, whereas the levels found in 30 patients with metastasis were between 25 and 71.8 units. The tissue origin of abnormal levels of serum glycosyltransferases and 5'-nucleotidase was discussed in relation to their physiological significance as well as their role as markers for diagnosing early malignant breast neoplasm and for monitoring the extent of metastasis.     

Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status.

PURPOSE: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. In breast cancer, tumor VEGF has been shown to have a good correlation with relapse-free survival. The aim of this study was to determine the relation of serum VEGF levels to the various indices of breast cancer and known tumor markers carcinoembryonic antigen and CA15.3. EXPERIMENTAL DESIGN: Preoperative serum VEGF levels were determined in 200 women with breast cancer and compared with serum VEGF levels in 88 healthy female controls. RESULTS: The serum VEGF levels of the cancer patients as a group were significantly elevated compared with those of the controls (P < 0.0005). VEGF levels were elevated in patients with invasive cancer of ductal/no specific type, ductal carcinoma in situ, and estrogen receptor (ER)-positive tumors. Patients with lobular carcinoma and ER-negative tumors had serum VEGF levels comparable with those in the controls. VEGF was more sensitive than CA15.3 and carcinoembryonic antigen in detecting breast cancer. CONCLUSIONS: Preoperative serum VEGF detects breast cancer with a sensitivity of 62.1%. The relationship to cancer type and ER status may have future therapeutic implications. Additional long-term studies are required to determine the prognostic significance of serum VEGF.     

Human kallikrein 6: a new potential serum biomarker for uterine serous papillary cancer.

PURPOSE: The discovery of novel biomarkers might greatly contribute to improve clinical management and outcomes in uterine serous papillary carcinoma (USPC), a highly aggressive variant of endometrial cancer. EXPERIMENTAL DESIGN: Human kallikrein 6 (hK6) gene expression levels were evaluated in 29 snap-frozen endometrial biopsies, including 13 USPC, 13 endometrioid carcinomas, and 3 normal endometrial cells by real-time PCR. Secretion of hK6 protein by 14 tumor cultures, including 3 USPC, 3 endometrioid carcinoma, 5 ovarian serous papillary carcinoma, and 3 cervical cancers, was measured using a sensitive ELISA. Finally, hK6 concentration in 79 serum and plasma samples from 22 healthy women, 20 women with benign diseases, 20 women with endometrioid carcinoma, and 17 USPC patients was studied. RESULTS: hK6 gene expression levels were significantly higher in USPC when compared with endometrioid carcinoma (mean copy number by real-time PCR, 1,927 versus 239, USPC versus endometrioid carcinoma; P < 0.01). In vitro hK6 secretion was detected in all primary USPC cell lines tested (mean, 11.5 microg/L) and the secretion levels were similar to those found in primary ovarian serous papillary carcinoma cultures (mean, 9.6 microg/L). In contrast, no hK6 secretion was detectable in primary endometrioid carcinoma and cervical cancer cultures. hK6 serum and plasma concentrations (mean +/- SE) among normal healthy females (2.7 +/- 0.2 microg/L), patients with benign diseases (2.4 +/- 0.2 microg/L), and patients with endometrioid carcinoma (2.6 +/- 0.2 microg/L) were not significantly different. In contrast, serum and plasma hK6 values in USPC patients (6.1 +/- 1.1) were significantly higher than those in the noncancer group (P = 0.006), benign group (P = 0.003), and endometrioid carcinoma patients (P = 0.005). CONCLUSIONS: hK6 is highly expressed in USPC and is released in the plasma and serum of USPC patients. hK6 may represent a novel biomarker for USPC for monitoring early disease recurrence and response to therapy.