Metabolic efficiency of the liver in patients with breast cancer as determined by pharmacokinetics of phenazone

Phenazone pharmacokinetics was determined in 24 healthy women and in 39 women with breast cancer; in the latter before and after antineoplastic treatment. The mean phenazone half-life time (t0.5) was significantly shorter in patients with breast cancer (8.880 +/- 2.5585 h) than in healthy persons (12.024 +/- 3.8486 h, P less than 0.001). Mean elimination rate constant (K, 0.063 +/- 0.0197 h-1) and mean metabolic clearance rate (MCR, 54.968 +/- 20.3476 ml/min) differed statistically (P less than 0.01) from the same parameters in control group, where K was 0.063 +/- 0.0197 h-1, MCR was 41.832 +/- 14.7153 ml/min. In patients receiving antineoplastic drugs, pharmacokinetic parameters of phenazone did not differ significantly in comparison with the initial values. Our results obtained with phenazone as a model substance suggest that in breast cancer elimination of other drugs metabolized by the pathway similar to phenazone also may be changed. This should be considered in selection of their dosage.     

Ornithine decarboxylase activity, prolactin blood levels, and estradiol and progesterone receptors in human breast cancer

Ornithine decarboxylase (ODC) activity in human breast cancer tissues was correlated with prolactinemia (Prl), estradiol and progesterone cytosol receptors (ER and PR), and histopathologic pattern. Ninety-two cases of breast cancer, six benign mammary disease, and three normal breast tissues were studied for ER, PR, and ODC. Prolactinemia was assessed in 59 cancer patients, 14 of whom showed hyper-Prl along with significantly higher ODC than in patients with normal-Prl [(20.01 +/- 6.33) 10(-2) vs (5.20 +/- 0.90) 10(-2) pmol CO2/micrograms protein/h; P less than 0.0125]. A direct correlation was found between Prl and ODC in postmenopausal women (n = 40). Prl was assayed in seven of 13 ER-PR breast cancer patients; a highly significant, direct correlation was found between Prl and ODC in this group (r = 0.934, P less than 0.0025). ODC did not correlate with ER or PR. Carcinomas with higher ODC (n = 17) had higher cellularity, lower histologic differentiation, and higher nuclear anaplasia than those in which ODC was not detectable (n = 13). In normal breast and five of six benign mammary disease tissues, ODC was not detectable. These findings suggest that ODC could be a reliable marker for prognosis.     

乳腺肿块超声造影增强强度与病理微血管密度的相关性

目的 研究声诺维超声造影对乳腺肿块增强强度与病理微血管密度(MVD)的相关性.方法 应用超声造影技术观察38例乳腺肿块微血管灌注情况,计算机定量测量肿块增强强度,对比良恶性肿瘤的造影强度特征,术后标本进行抗Ⅷ因子免疫组化染色,测量MVD.结果 乳腺肿块超声造影增强强度与病理MVD有较好的相关性(r=0.802,P＜0.005),造影强度与MVD恶性组均大于良性组.结论 声诺维超声造影有助于鉴别诊断乳腺良恶性肿瘤及评估乳腺癌的预后.     

Sigma S, a measure of reactive sulfur groups of immunoglobulin G, is a sensitive tumor marker discriminating different stages of breast cancer

Sigma S is a measure of the disulfide bonds and free thiol groups of serum immunoglobulin (Ig) G, as determined by the reaction with dithionitrobenzoate. Significant decreases of sigma S previously were detected in malignant compared with benign diseases of various organs. This study shows the application of sigma S for the diagnosis of breast cancer. The following results were obtained. First, 132 patients with benign breast diseases showed a sigma S of 1.48 +/- 0.29 (standard deviation) per mole IgG; this was not different from 1.51 +/- 0.36 found in 182 controls. In contrast, IgG from 198 patients with primary breast carcinoma of all four stages (tumor-node-metastasis system) gave a sigma S of 1.22 +/- 0.29, a significant (P less than 0.0001) decrease of sigma S from benign to malignant breast disease. Second, sigma S values of single Stages I, II, III, and IV, were 1.27 (n = 59), 1.23 (n = 83), 1.19 (n = 35), and 1.10 (n = 21), respectively, each significantly different from sigma S in benign disease and showing a decreasing trend with increasing tumor progress. Differences were significant between Stages I and IV (P less than 0.025) and II and IV (P less than 0.05). Third, 63% of Stage I breast carcinoma patients had sigma S values below a critical threshold of 1.38. This serum positivity rose to 90% in Stage IV. These values exceeded those reported with other tumor markers. The overall power of sigma S to distinguish between benign and malignant breast disease had a specificity of 61% and a sensitivity of 78%. Early stages (I and II) of breast cancer could be distinguished from benign diseases with 64% specificity and 69% sensitivity. Advanced Stage IV could be discriminated from early Stages I and II with 55% specificity and 71% sensitivity. Thus, the analysis of sigma S may significantly contribute to the surveillance of patients with breast cancer.     

乳腺癌血清VEGF水平与癌组织中VEGF和COX-2表达及微血管密度的关系

目的探讨乳腺癌患者血清血管内皮生长因子(sVEGF)水平与乳腺癌血管生成的关系。方法采用酶联免疫吸附试验(ELISA)检测68例乳腺癌、35例乳腺良性病变和20例健康女性的sVEGF水平,免疫组化S-P法检测相应乳腺癌组织中VEGF、环氧合酶-2(COX-2)及微血管密度(MVD)表达水平,并分析sVEGF水平与VEGF、COX-2及MVD表达的关系。结果(1)健康女性组、乳腺良性病变组和乳腺癌组sVEGF浓度中位数分别为105.93、150.82和306.51 pg/ml,乳腺癌组明显高于健康女性组。(2)乳腺癌组VEGF和COX-2表达阳性率分别为67.6%和44.1%,乳腺良性病变组VEGF和COX-2表达阳性率分别为42.9%和11.4%,两组间差异有统计学意义(P值分别为0.015和0.002)。(3)乳腺癌患者sVEGF水平与癌组织中VEGF、COX-2及MVD表达均呈正相关。(4)乳腺癌患者中,VEGF表达阳性组COX-2阳性率(65.21%)明显高于VEGF表达阴性组(18.18%); COX-2表达阳性组MVD(22.94±5.51)明显高于COX-2表达阴性组(10.30±4.42)。结论乳腺癌患者sVEGF水平明显增高于健康女性,并与癌组织中VEGF、COX-2及MVD表达呈正相关。     

N(1),N(12)-Diacetylspermine as a sensitive and specific novel marker for early- and late-stage colorectal and breast cancers.

PURPOSE: N(1),N(12)-diacetylspermine (DiAcSpm) in the urine of colorectal and breast cancer patients was examined to establish its usefulness as a novel diagnostic tool for detecting these cancers at clinically early stages. EXPERIMENTAL DESIGN: Urine samples from 248 colon cancer patients and 83 breast cancer patients as well as 51 patients with benign gastrointestinal diseases treated in Tokyo Metropolitan Komagome Hospital during the period of August 1999 to January 2004 were collected. DiAcSpm was analyzed by ELISA and its sensitivity for malignant conditions was compared with that of serum carcinoembryonic antigen (CEA), CA19-9, and CA15-3. RESULTS: The sensitivity of urinary DiAcSpm for colon cancer patients (n = 248) was 75.8% (mean +/- 2 SD for 52 healthy controls as a cutoff value), which was markedly higher than the sensitivities of serum CEA (39.5%, P < 0.0001) and CA19-9 (14.1%, P < 0.0001). DiAcSpm was elevated in 60% of tumor-node-metastasis cancer stage 0 + I patients, whereas only 10% (P < 0.0001) and 5% (P < 0.0001) of these patients were CEA- and CA19-9-positive, respectively. The sensitivity of urinary DiAcSpm for 83 cases of breast cancer (60.2%) was higher than the sensitivities of CEA (37.3%, P = 0.0032) and CA15-3 (37.3%, P = 0.0032). DiAcSpm was elevated in 28% of tumor-node-metastasis stage I + II patients, whereas only 3% (P = 0.0064) and 0% (P = 0.001) of these patients were CEA- and CA15-3-positive, respectively. CONCLUSION: The observations indicate that urinary DiAcSpm is a more sensitive marker than CEA, CA19-9, and CA15-3 and that it can efficiently detect colorectal and breast cancers at early stages.     

SRC kinase and mitogen-activated protein kinases in the progression from normal to malignant endometrium.

PURPOSE: The purpose of this research was to determine whether a correlation exists between the levels of activated mitogen-activated protein kinase (MAPK) and Src kinases and the progression from normal to malignant endometrium. EXPERIMENTAL DESIGN: We measured total and phosphorylated levels for extracellular signal-regulated kinase 1/2, p38, stress-activated protein kinase/c-Jun NH(2)-terminal kinase, and Src kinases from 33 frozen endometrial adenocarcinomas and 38 benign endometrial specimens by quantitation of signals from Western blots using antibodies against these kinases. RESULTS: Elevated phospho-extracellular signal-regulated kinase 1/2 (150 +/- 40 versus 46 +/- 7; P = 0.03), phospho-Src (28 +/- 5 versus 4 +/- 1), and phospho-p38 (131 +/- 16 versus 27 +/- 7; P < 0.001) was detected in benign versus malignant endometrium when the Western blot signal of activated kinase was normalized to total kinase levels and beta actin. A modest increase in active c-Jun NH(2)-terminal kinase was detected in carcinoma versus benign specimens (51 +/- 13 versus 43 +/- 10; P = 0.8). Expression of total kinases (normalized to beta-actin) was higher in carcinoma versus benign specimens, respectively (extracellular signal-regulated kinase 1/2, 9 +/- 2 versus 0.7 +/- 0.1; Src, 7 +/- 2 versus 0.4 +/- 0.1; stress-activated protein kinase c-Jun NH(2)-terminal kinase, 2 +/- 0.4 versus 0.2 +/- 0.02; P < 0.001; and p38, 1 +/- 0.2 versus 0.4 +/- 0.1; P < 0.01). Immunohistochemistry for active and total Src kinases and MAPKs detected positive staining in epithelial and stroma cells. CONCLUSIONS: These data demonstrated that, in contrast with breast cancer, the progression from normal to malignant endometrium is not associated with activation of MAPK and Src kinases. Elevation of these active kinases in benign endometrium may contribute to endometrial resistance to the antiestrogen action of tamoxifen.     

Nipple fluid basic fibroblast growth factor in patients with breast cancer.

PURPOSE: It has been shown that early detection of breast cancer could save lives. Recently, there has been increasing interest in nipple fluid as a potential supplemental avenue for breast cancer diagnosis. EXPERIMENTAL DESIGN: In this study, we determined the levels of an angiogenic factor basic fibroblast growth factor (bFGF) in the nipple fluid of healthy subjects as well as patients with benign breast conditions, those at high risk for breast cancer, and patients with active breast cancer. ELISAs were used to measure bFGF. RESULTS: Nipple fluid bFGF levels were as follows (mean +/- SE): 158 +/- 17 pg/mL from benign breasts, 561 +/- 277 pg/mL from high-risk breasts, and 1,343 +/- 441 pg/mL from cancerous breasts. One-way ANOVA showed that the bFGF levels from cancerous breasts were significantly higher than those from benign and high-risk breasts (P = 0.0001 and P = 0.0193, respectively). After logarithmic transformation was applied to the data, high-risk breast bFGF levels were higher than those from benign breasts (P = 0.0028). With a cutoff level of 250 pg/mL, the sensitivity was 79.2%, specificity was 82.5%, and correct diagnosis was 66.4%. The area under the receiver operating characteristic curve was 0.86. CONCLUSIONS: We conclude that nipple fluid bFGF levels are progressively elevated in high-risk and cancerous breasts compared with benign breasts. The sensitivity and specificity of this test are promising compared with current breast cancer screening methods, and this test deserves further studies with larger clinical trials. Potential areas of usefulness include the detection of breast cancer risk or breast cancer, as well as the monitoring and/or prediction of the antiangiogenic effect of preventive therapies.     

CT灌注成像在肺部肿物诊断及鉴别诊断中的应用研究

背景与目的:良、恶性肿瘤的血流供应与代谢在质、量上有着明显的差异,目前正在开发使用新的影像学技术来鉴别恶性、良性结节的血供情况,灌注成像技术是其中一种.本文采用多层螺旋CT灌注成像技术,定量评价肺内块状病灶的血流特点及其对良、恶性肿瘤进行鉴别诊断的价值.方法:52例初诊为肺部肿物的患者(37例恶性、7例良性、8例活动性炎性),行16排螺旋CT灌注扫描.利用功能软件包自动获取动、静脉、病灶的时间-密度曲线及病变的灌注参数,包括灌注量(perfusion volume,PV)、血容量(blood volume,BV)、对比剂平均通过时间(mean transit time MTT)、增强峰值(peak height,PH).结果:恶性、活动性炎性、良性病变PV值分为(27.63±15.06)ml·min-1·ml-1、(30.80±20.33)ml·min-1·ml-1、(11.81±3.74)ml·min-1·ml-1,PH值分别为(28.46±12.07)Hu、(32.15±15.89)Hu、(10.41±3.77)Hu,BV分别为(21.64±10.97)ml/100 g、(28.38±14.55)ml/100 g、(10.61±5.33)ml/100 g,恶性及活动性炎性病变这3值均显著高于良性病变.恶性、活动性炎性、良性病变的MTT值分别为(28.39±21.66)s、(25.91±14.57)s、(29.86±13.57)s,三者差异没有统计学意义.恶性、活动性炎性病变间4个灌注参数均没有统计学差异.若以PV值＞20 ml·min-1·ml-1,且PH＞15 Hu作为鉴别恶性、良性病变(除外活动炎性病变)的阈值,其灵敏度、特异度、准确性分为91.9%、100%、84.1%.结论:多层螺旋CT灌注成像能定量评价肺部肿物血流模式,可用于无创性诊断和鉴别诊断肺部病变.     

Vascular endothelial growth factor levels in ovarian cyst fluid correlate with malignancy.

Ovarian cancer is a richly vascularized neoplasm with solid and cystic components. The purpose of this study was to determine whether cyst fluid could be used to quantitatively evaluate production of angiogenic factors in ovarian lesions. ELISA was used to measure vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cyst fluid of patients with ovarian cancer (n = 13), benign cysts and cystadenomas (n = 23), borderline tumors (n = 5), and functional cysts (n = 8). VEGF levels were markedly elevated in the fluid of malignant cysts (38.5+/-8.2 ng/ml) as compared with benign (1.6+/-0.4 ng/ml; P < 0.001), borderline (5.7+/-1.5 ng/ml; P < 0.001), or functional cysts (3.8+/-2.0 ng/ml; P < 0.001). The presence of VEGF in cancer cells was confirmed by immunohistochemistry. Follow-up of patients with malignant and borderline lesions demonstrated a correlation between VEGF levels in cyst fluid and tumor recurrence (P = 0.03). bFGF in malignant cysts was either undetectable or very low (0.3+/-0.2 ng/ml), and no significant differences were found in bFGF levels among malignant, benign, borderline, and functional cysts. This study demonstrates that ovarian malignancy is associated with dramatic elevation of VEGF levels in ovarian cyst fluid. Conversely, there is no correlation between cyst fluid bFGF levels and malignant transformation. The high levels of VEGF in malignant cysts are consistent with the hypothesis that this growth factor plays an important role in ovarian cancer related-angiogenesis and tumor progression and represents a potentially important target of antiangiogenic therapy.     

Cathepsin D in breast secretions from women with breast cancer.

A proteinase accumulated in breast secretions from women with breast cancer has been characterised. Inhibition of the proteolytic activity of breast secretions by pepstatin A showed that the main enzyme involved was an aspartyl proteinase. Determination of its cleavage specificity by SDS-PAGE and amino acid sequence analysis revealed that it was identical to that of cathepsin D, an aspartyl proteinase suggested to be involved in breast cancer development. The identity between both proteins was further confirmed by immunological analysis with monoclonal antibodies against cathepsin D. Quantification of cathepsin D in nipple fluids from 41 women with benign or malignant breast diseases and from 19 control women without breast pathology revealed the presence of variable amounts of this proteinase. The average concentration of cathepsin D in breast secretions from cancer-bearing breasts was 7.2 +/- 2.2 fmol micrograms of protein, which was significantly higher than those of nipple fluids from control women (2.9 +/- 0.6 fmol micrograms-1) (P = 0.04) or from patients with benign breast diseases (2.1 +/- 0.3 fmol micrograms-1) (P = 0.004). Though the number of cancer patients studied was small (n = 21), no correlations were found with cytosolic concentrations of cathepsin D or oestrogen receptors, neither with other parameters such as tumour size, histological grade, axillary node involvement or menopausal status.     

三种检查方法对乳腺疾病的诊断价值

目的探讨三算子扫描仪、多普勒彩色超声及钼靶X线摄影对乳腺疾病的诊断价值。方法对578例经手术和病理检查证实的乳腺良、恶性疾病患者术前均采用三算子扫描、彩超及X线进行诊断。结果对于乳腺增生性疾病、乳腺癌三种检查方法诊断符合率在87.61%～91.91%之间,三者间无统计学意义（P〉0.05）;对于乳腺良性肿瘤的诊断符合率彩超优于X线（P〈0.05）。对于≤35岁乳腺癌的诊断符合率三算子、彩超均优于X线（P〈0.05）,对于35～50岁乳腺癌三者之间无差别（P〉0.05）,对于≥50岁乳腺癌X线明显优于三算子、彩超（P〈0.05）。对于肿块〈2 cm的乳腺癌诊断符合率三算子、彩超优于X线（P〈0.05）,而对于无肿块仅伴有恶性钙化征象的诊断符合率X线明显优于三算子（P〈0.05）。结论三种检查方法对乳腺良、恶性疾病都有较高的诊断价值,且对于乳腺癌的诊断具有互补性。X线适合50岁以上以及有恶性钙化灶的患者,彩超适合于各种类型的乳房,可弥补X线的不足,三算子对乳腺疾病的敏感性、准确性与彩超相当。     

Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors

Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data.     

Uptake of 11C-methionine in breast cancer studied by PET. An association with the size of S-phase fraction.

L-[methyl-11-C]methionine (11C-methionine) uptake of seven primary breast cancers, four soft tissue metastases of breast cancer, and three other breast lesions was studied by positron emission tomography (PET). 11C-methionine accumulation was assessed by calculating the standardised uptake value (SUV). The mean SUV for breast cancer was 8.5 +/- 3.3 (s.d.), while the maximal uptake in the liver was 12.4 +/- 1.6, in the bone marrow 5.8 +/- 0.7, and in the myocardium 3.4 +/- 0.6. All eight malignant tumours larger than 30 mm in diameter accumulated clearly 11C-methionine, whereas none of the three smaller cancers (from 12 to 15 mm in diameter) were visualised. Strong uptake of 11C-methionine was associated with a large S-phase fraction (SPF) measured with flow cytometry (r = 0.77, P = 0.01), and the non-visualised cancers had all a small SPF (less than 5.5%). One benign tumour (an abscess) accumulated slightly 11C-methionine. The results indicate that both primary and metastatic breast cancer can be effectively imaged with 11C-methionine by PET, and that the accumulation of 11C-methionine may correlate with the proliferation rate of breast carcinoma.     

Argyrophilic nucleolar organizer regions of breast tumors: Assessment of aspirated cytological materials

To investigate the correlation between argyrophilic nucleolar organizer regions (Ag-NORs)and the malignant potential of breast tumors, we analyzed Ag-NORs of cytological specimens obtained from 190 patients with various types of breast disease by preoperative aspiration biopsy. The average number of Ag-NORs per nucleus was defined as the Ag-NOR score. The Ag-NOR score was 5.7 +/- 1.7 in the group of women with breast carcinoma (n =70), 2.6= 0.4 in the group with fibroadenoma (n= 54) and 2.9= 0.6 in the group with mastopathy (n= 66). The level was significantly higher in breast carcinoma than in each benign disease(P < 0.001 in both cases). The score was 6.5 +/- 2.3 in the group with four or more metastatic lymph nodes (n = 21), 5.2+/- 1.2 in the group with one to three metastatic lymph node (n= 10) and 5.1+/- 1.1 in that with no metastatic lymph node (n = 39);the score was significantly (P < 0.05) higher in the groups with four or more metastatic lymph modes than in the other groups, respectively. Thus, a correlaton was observed between the Ag-NOR score and lymph node status. These data suggest that a higher Ag-NOR score reflects high-grade malignancy.     

Evaluation of tumor marker CA15-3 in breast cancer

CA15-3, a new tumor marker for breast cancer, was determined in various malignant diseases including breast cancer and various benign diseases, and its clinical significance and usefulness were studied. In 18 normal individuals, the value of CA15-3 was 8.9 +/- 3.3 U/ml (mean +/- SD). In primary breast cancer, the positivity was 20% for Stage I, 0% for Stages II and III and 100% for Stage IV. Of 17 cases of recurrent breast cancer, 13 (77%) were shown to be positive. The therapeutic effect and the value of CA15-3 were well correlated with each other. As for other malignant tumors, positive cases were observed in 50% of recurrent cancer of the stomach and in 14% of malignant tumors of the biliary system. All of these cases were terminal-stage cancers. The CEA value determined simultaneously showed a good correlation, r = 0.87 (p less than 0.01) with CA15-3 in malignant tumors other than breast cancer. In breast cancer, however, the correlation between the two was low, r = 0.18. These results suggest that CA15-3 is not necessarily useful in the diagnosis of primary breast cancer, but is useful as an indicator of the effect of therapy for recurrent breast cancer and for the prediction of recurrence.     

Transvaginal color Doppler ultrasonic characterization of benign and malignant ovarian cystic teratomas and comparison with serum squamous cell carcinoma antigen

BACKGROUND: The preoperative diagnosis of squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary remains difficult. The purpose of this study is to examine the usefulness of transvaginal color Doppler ultrasound (TV-CDU) in differentiating malignant (SCC) from benign cystic teratoma of the ovary. METHODS: Eighty-eight patients with an ovarian tumor showing gray scale sonographic appearances of mature cystic teratoma were preoperatively evaluated for the presence or absence of intratumoral blood flow by TV-CDU. The blood flow characteristics of the tumor vessels were analyzed using the resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV). The serum levels of SCC antigen were also randomly examined preoperatively in 50 patients. RESULTS: Intratumoral blood flow was significantly detected in malignant teratomas (SCCs) (80.0%; 4 of 5) compared with benign teratomas (20.5%; 17 of 83) (P < 0.01). All malignant teratomas with intratumoral blood flow showed both RI less than 0.4 and PI less than 0.6, whereas no benign teratomas showed any such value except for 1 case with struma ovarii. In addition, both the mean RI and the mean PI values in the tumor vessels were significantly lower in the malignant teratomas (RI: 0.31 +/- 0.07; PI: 0.40 +/- 0.16) than in the benign teratomas (RI: 0.62 +/- 0.13; PI: 1.06 +/- 0.44) (P < 0.001). However, the mean PSV value of the malignant teratomas (PSV: 20.6 +/- 8.33) was not significantly different from the benign teratomas (PSV: 18.1 +/- 9.9). Elevation of serum SCC was found in 4 of 5 patients (80%) with malignant teratomas, whereas the elevation was found in 11 of 45 patients (24.4%) with benign teratomas (P < 0.05). The diagnostic accuracy using the RI (cutoff value 0.4) as well as the PI (cutoff value 0.6) was thus 95.2%, which was significantly superior to that obtained by using the serum SCC (76%) (cutoff value, 1.5 ng/mL). CONCLUSIONS: Evaluating the presence or absence of intratumoral blood flow, together with blood flow resistance, in tumor vessels using TV-CDU thus may be more useful to differentiate malignant (SCC) from benign cystic teratomas of the ovary than by measuring serum SCC levels.     

Diagnostic significance of the tumour markers CEA, CA 15-3 and CA 125 in malignant effusions in breast cancer

Concentrations of the tumour-associated antigens CEA, CA 15-3 and CA 125 were determined in serous effusions (EF) from patients (pts) with breast cancer. As controls, serous effusions from patients with benign and other malignant diseases were used. The EF levels were also compared with those of serum. CA 15-3 was elevated (greater than 35 U/ml) in 65.7% of breast cancer EF, in 39.3% of EF in various other malignant diseases and in 0% of benign EF. CEA was elevated (greater than 9 ng/ml) in 37.5% of breast cancer EF, in 17.9% of EF of various other malignant diseases and in 27% of benign EF. CA 125 was elevated (greater than 35 U/ml) in 93.8% of breast cancer EF, in 78.6% of EF of various other malignant diseases and in 58.8% of benign EF. There was a statistically significant correlation between EF and serum values for the markers studied. Sensitivity and specificity for CA 15-3 were 65.7% and 76.6%, for CEA 37.5% and 77.7% and for CA 125 93.8% and 28.7%, respectively. CA 15-3 is a marker with definite diagnostic accuracy compared to CEA and CA 125 in breast cancer EF. CA 125 appears to derive from proliferating mesothelia rather than cancer cells alone and occurs in a broad spectrum of malignant as well as benign EF. The above markers should not be used alone for diagnosis of breast cancer in patients with serous effusions.     

Elevation of serum riboflavin carrier protein in breast cancer.

Presently available tumor markers have had a limited clinical impact. Riboflavin carrier protein (RCP) is an estrogen inducible protein that occupies a key position in riboflavin metabolism. Because other vitamin carrier proteins (VCP) have been shown to be overexpressed in patients with malignant disease, we evaluated serum RCP levels in patients with adenocarcinoma of the breast. In this prospective blinded study, patients with breast cancer, benign breast disease, and healthy controls were analyzed for RCP levels. Using a highly sensitive RIA, we observed that serum RCP levels were significantly elevated in women with breast cancer (n = 52) as compared with control subjects [n = 50; 6.06 +/- 7.27 ng/ml versus 0.70 +/- 0.19 ng/ml (mean +/- SD), respectively; P < 0.0001]. A serum RCP level of > or = 1.0 ng/ml was highly predictive of the presence of breast cancer, detecting 88% of tumors in stages I-II and 100% of tumors in stages III-IV. Overall, this RCP assay has a sensitivity of 92.3%, a specificity of 88%, a positive predictive value of 88.9%, and a negative predictive value of 91.7%. These results show increased serum levels of RCP in breast adenocarcinoma patients and suggest that RCP levels may be useful as a new marker for breast cancer. The positive predictive value in early-stage breast cancer suggests that the RCP assay may be a useful adjunct to present screening technology.     

Technetium-99m methylene diphosphonate scintimammography for evaluation of palpable breast masses

Technetium-99m-methylene diphosphonate (Tc-99m MDP) scintimammography (SMB) was used to investigate palpable breast masses during routine presurgical bone scintigraphy, for women at high risk for cancer and who were candidates for surgery or excisional biopsy. Upright anterior and prone lateral views of the breasts were acquired from 65 women with palpable breast masses, 5-10 min after intravenous injection of 740 MBq of Tc-99m MDP. Breast cancer was histologically diagnosed in 50 women (77%) and benign disease was found in 15 women (23%). Of these 50 breast cancer patients, 44 (88%) showed abnormal MDP uptake in breasts. Among the 15 cases of benign lesions, only 1 (7%) showed abnormal MDP uptake in the breasts. The diagnostic sensitivity, specificity, and accuracy were 88%, 93%, and 89%, respectively, for the differentiation of malignant and benign breast masses. Scintimammography with Tc-99m MDP is a useful and cost-effective tool for differentiating malignant breast masses from benign breast masses.