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.     

血清唾液酸检测对癌症诊断的临床价值

作者测定了５７７例正常人和２４１例恶性肿瘤患者血清总唾液酸（ＴＳＡ）和血清脂质结合唾液酸（ＬＳＡ）的含量。结果表明：ＴＳＡ和ＬＳＡ的含量变化与疗效一致，治疗有效者ＴＳＡ和ＬＳＡ与正常人相比，均无显著性差异（Ｐ＞０．０５）；治疗无效（包括未经治疗）者与正常人相比除原发性肝癌、乳腺癌外均有显著性差异（Ｐ＜０．０１）。血清ＴＳＡ和ＬＳＡ测定对肺癌、胃癌、大肠癌等有临床诊断价值（Ｐ＜０．０１），对鼻咽癌诊断效果更好（Ｐ＜０．００１）。对肝癌、乳腺癌的诊断价值有限（Ｐ＞０．０５）。恶性肿瘤患者ＴＳＡ与ＬＳＡ含量间无相关关系（ｒ＝０．０９；Ｐ＞０．０５；ｎ＝１１７）。ＬＳＡ检测不能代替ＴＳＡ检测，两者应该联合检测以提高其阳性率。     

Serum glycoconjugates in patients with anemia and myeloid leukemia

Because of carbohydrate alterations in malignant cells, serum glycoproteins have drawn considerable attention. In the current investigation we determined total sialic acid (TSA), lipid bound sialic acid (LSA), protein bound hexoses (galactose + mannose), fucose, hexosamines (galactosamine + glucosamine) and mucoid protein concentrations in the serum of patients with anemia and myeloid leukemia. The results were compared with those obtained in healthy individuals. In the leukemia patients we observed significant increases in glycoconjugates compared with the controls (P less than 0.001), and in TSA and fucose levels compared with the anemia patients (P less than 0.001). LSA and hexosamine levels were significantly lower in anemia patients with respect to the leukemia patients (P less than 0.01 and P less than 0.05 respectively), whereas levels of mucoid proteins and hexoses did not show significant differences. Except for hexosamines, all the markers tested were significantly elevated in the anemia patients compared with the controls. The present study suggests that the glycoconjugates investigated might be useful biochemical markers for differentiating anemic from leukemic conditions.     

Total and lipid-bound sialic acid in the cerebrospinal fluid of patients with brain tumors

Total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in the cerebrospinal fluid (CSF) from 63 patients with various neurological diseases. Of these, 27 had brain tumors: 20 had glioma, and 7 pituitary adenoma. TSA levels were significantly increased in the CSF of 18 of the 20 glioma patients (p less than 0.001), while in the adenoma patients were indistinguishable from the controls; with a 90 and 0% test sensitivity respectively. Conversely, the LSA concentrations were significantly elevated, both, in the glioma and pituitary adenoma patients (p less than 0.001), with a 68 and 100% test sensitivity respectively. These preliminary data suggest that measurement of TSA and LSA in the CSF should prove useful for the diagnosis of brain tumors and, perhaps, in the follow-up of patients undergoing treatment for brain tumors.     

Five tumor markers in lung cancer: significance of total and "lipid"-bound sialic acid.

Total sialic acid (TSA) and "lipid-bound" sialic acid (LSA) were evaluated in comparison to carcinoembryonic antigen (CEA) and ferritin and neuron specific enolase (NSE) in 152 untreated patients with primary lung cancer, 107 benign pulmonary disease patients and 207 notmal controls. The mean concentrations of TSA, LSA and CEA in lung cancer patients, were significantly higher than in benign and normal controls (p less than 0.001), while the mean ferritin and NSE levels were significantly higher than in normal controls only (p less than 0.001). At the designated cut-off serum levels, sensitivities of the five markers for lung cancer were in decreasing order: TSA 86.5% (greater than 80 mg/dL), LSA 77% (greater than 20 mg/dL), CEA 46.4% (greater than 5 ng/mL), ferritin 36% (greater than 300 ng/mL) and NSE 34.5% (greater than 12.5 ng/mL). Using the benign pulmonary values as negative controls the specificity of each marker was as follows: CEA 88%, ferritin 72%, NSE 58%, TSA 44% and LSA 44%. In small cell lung cancer (SCLC) patients, NSE mean concentrations and sensitivity were significantly higher than in non-small lung cancer (NSCLC) patients (9.63 +/- 4.4 versus 23.54 +/- 16.9, p less than 0.001 and 74% versus 21.4% respectively). While in NSCLC patients only CEA levels correlated well with the stage of the disease, in SCLC patients concentrations of TSA, LSA and ferritin were significantly higher in extensive than in limited disease stages. These preliminary data suggest that, although TSA and LSA are highly sensitive markers in lung cancer, their specificity is low.     

Diagnosis Value of Membrane Glycolipids Biochemistry Index in Intracranial and Gastrointestinal Tumors

The diagnostic value of membrane glycolipid biochemistry index, the lipid-bound sialic acid (LSA) and totalsialic acid (TSA) in cerebrospinal fluid (CSF) was evaluated in 30 intracranial and 65 gastrointestinal tumors.The plasma LSA, TSA and red cell membrane sialic acid (R-SA) in were determined according to the method ofSevenmerhulm. Our results showed that the levels of LSA and TSA in CSF of intracranial tumor patients washigher than that of normal group(p<0.01). The concentration of TSA and LSA in patients with malignant gliomawas higher than that of benign meningioma patients(P<0.01). No significance was found between intracranialhalmatoma patients and normal control group for levels of membrane glycolipids (p>0.05). Results also found thatthe plasma LSA, TSA and R-SA of gastric carcinoma were significantly higher than those of control group (p<0.05);while no significant difference was found in the plasma LSA, TSA and R-SA levels between chronic gastritis,gastrohelcoma and normal control group (p>0.05). Plasma LSA, TSA and R-SA levels of gastric carcinoma patientwere significantly higher than those of chronic gastritis patients and gastrohelcoma patients(p<0.05). It was alsofound that plasma LSA, TSA and R-SA contents were significantly higher in large intestine carcinoma patientsthan in benign in stestine tumor patients (p<0.05) while no significant difference was found between intestinebenign tumor and normal control group (p>0.05). The levels of LSA, TSA and R-SA were obviously higher inthe patients with metastasis than in the ones without (p<0.05.) The membrane glycolipid biochemistry indexLSA and TSA in CSF are sensive markers for diagnosing intracranial tumors. For gastrointestinal malignanttumors the plasma LSA TSA and red blood cell membrane SA may be considered as auxiliary indicators fordiagnosis. They can be used for distinguishing benign from malignant tumors.     

Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity

Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease.     

Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy

To determine the influence of infiltrating lobular histology on local tumor control, the authors studied 49 patients with Stages I and II infiltrating lobular breast carcinoma treated by limited excision of the tumor and radiotherapy between 1968 and 1981 (median follow-up, 75 months). Results were compared with those in 561 cases of infiltrating ductal carcinoma similarly treated during the same period. The 5-year actuarial risk of local recurrence was similar for patients with infiltrating lobular or ductal carcinoma when the latter was evaluated as a single group (12% versus 11%). However, the 12% 5-year actuarial local recurrence risk for patients with infiltrating lobular carcinoma was intermediate between that for patients with infiltrating ductal carcinomas with an extensive intraductal component (23%) and those without an extensive intraductal component (5%). The pattern of recurrence in the breast was similar in the infiltrating lobular and ductal groups. All recurrences in patients with infiltrating lobular carcinoma and 80% of recurrences in the infiltrating ductal group occurred in the vicinity of the primary tumor (P = not significant). None of the clinical or morphologic features examined significantly influenced the risk of local recurrence in patients with infiltrating lobular carcinoma. The authors conclude that combined conservative surgery and radiotherapy appear to be a reasonable treatment option for patients with infiltrating lobular carcinoma, but further follow-up will be required to confirm these results.     

Clinical evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

Spectral morphometric characterization of breast carcinoma cells

The spectral morphometric characteristics of standard haematoxylin and eosin breast carcinoma specimens were evaluated by light microscopy combined with a spectral imaging system. Light intensity at each wavelength in the range of 450-800 nm was recorded for 10(4) pixels from each field and represented as transmitted light spectra. A library of six characteristic spectra served to scan the cells and reconstruct new images depicting the nuclear area occupied by each spectrum. Fifteen cases of infiltrating ductal carcinoma and six cases of lobular carcinoma were examined; nine of the infiltrating ductal carcinoma and three of the lobular carcinoma showed an in situ component. The spectral morphometric analysis revealed a correlation between specific patterns of spectra and different groups of breast carcinoma cells. The most consistent result was that lobular carcinoma cells of in situ and infiltrating components from all patients showed a similar spectral pattern, whereas ductal carcinoma cells displayed spectral variety. Comparison of the in situ and the infiltrating ductal solid, cribriform and comedo carcinoma cells from the same patient revealed a strong similarity of the spectral elements and their relative distribution in the nucleus. The spectrum designated as number 5 in the library incorporated more than 40% of the nuclear area in 74.08% of the infiltrating lobular cells and in 13.64% of the infiltrating ductal carcinoma cells (P < 0.001). Spectrum number 2 appeared in all infiltrating ductal cells examined and in none of the lobular cells. These results indicate that spectrum number 5 is related to infiltrating lobular carcinoma, whereas spectrum number 2 is characteristic for infiltrating ductal carcinoma cells. Spectral similarity mapping of central necrotic regions of comedo type in situ carcinoma revealed nuclear fragmentation into defined segments composed of highly condensed chromatin. We conclude that the spectral morphometric features found for lobular and ductal cell populations may serve future automated histological diagnostics.     

Correlation of total (TSA) and lipid and bound (LSA) sialic acid levels with cytology of cyst or body fluids in cancer patients.

In this preliminary study, aiming at the early diagnosis or the confirmation of neoplastic spreading, the levels of sialic acid (TSA and LSA, total sialic acid and "lipid bound" sialic acid) were measured and correlated with the corresponding cytologic findings in 111 body or cystic fluid samples taken from patients with suspected or confirmed cancer. The samples were classified according to the body fluid origin: peritoneal (35), breast cyst (22), pleural (21), thyroid gland cyst (5), renal cyst (5), ovarian cyst (6), bronchial washing (3), douglasic cavity (3) and various other origins (11). It was found that 32.43% of the samples were TSA positive, 44.14% LSA positive, 20.75% cytologic and 8.49% cytology suspect (positive + suspect = 29.24%). Thus, the combination of a tumor biomarker with the corresponding cytology of the body fluid gives the best possible results, as regards both the confirmation of positive cytology and the detection of possible metastases, as well as the monitoring of the disease after treatment.     

Total and lipid-bound plasma sialic acid as diagnostic markers in colorectal cancer patients: correlation with cathepsin B expression in progression to Dukes stage

PURPOSE: Serum cathepsin B (CB), Total Sialic acid (TSA), total sialic acid (TSA) and lipid bound sialic acid (TSA) concentrations more useful than the other markers investigated for detecting different malignancies. Our aim was to investigate the possible correlation between serum CB with TSA, LSA in colorectal carcinoma with pathological stages progressed of the disease. METHODS: The study was performed on 177 patients (109 patients with colon and 68 patients with rectal) and 50 healthy individuals comprised the control group. Serum CB activity was determined using fluorogenic substrate. Serum TSA and LSA Concentrations were measured according to the method described by Katopodis. RESULTS: Plasma CB and TSA levels in the tumor group were significantly increased in comparison with the controls group (P < or = 0.0001). No significant differences were observed in LSA level between the tumor group and the controls group. T/N ratios for CB, TSA elevated 2.3-fold, 2.5-fold respectively). LSA 1.8-fold. Serum CB activity, TSA concentrations values in plasma samples of patients were increased significantly with pathological stages progressed (P < or = 0.0001). CB is seen to correlate more strongly with TSA in tumor group (P < or = 0.0001, r= 0.7277) in comparison with controls group. These correlations became more significant as the stage of the disease progressed. CONCLUSION: The present investigations indicate that CB activity, serum TSA, concentrations are sensitive markers for detecting and earliest diagnosis of colorectal cancer. These markers with other clinical and biochemical criteria may play important metabolic roles in cancer progression.     

Breast cancer detection by dedicated breast positron emission tomography according to the World Health Organization classification of breast tumors

ObjectiveConsidering the difficulty in detecting primary breast cancers using whole-body positron emission tomography (WBPET) owing to its limited spatial resolution, we aimed to evaluate the detectability of breast cancer by ring-type dedicated breast PET (DbPET) on the World Health Organization (WHO) histological classification in comparison with WBPET.MethodsA total of 938 patients with breast cancer underwent WBPET and ring-type DbPET, and 1021 lesions were histologically assessed based on the WHO classification of tumors of the breast. The findings of WBPET and DbPET were retrospectively evaluated and compared.ResultsThe size-related sensitivity of DbPET was superior to that of WBPET for subcentimetric tumors (81.9% vs. 52.4%, P < 0.001). The histological distribution was as follows: 11 lobular carcinoma in situ, 158 ductal carcinoma in situ, 738 infiltrating duct carcinoma not otherwise specified (NOS), 12 lobular carcinoma NOS, 40 mucinous adenocarcinoma, 13 tubular carcinoma, 36 invasive breast carcinoma others, and 13 papillary neoplasms. WBPET had low sensitivity for lobular carcinoma in situ, ductal carcinoma in situ, lobular carcinoma NOS, mucinous adenocarcinoma, and tubular carcinoma. DbPET showed improved sensitivity for all the above except lobular and tubular carcinoma. The maximum standardized uptake values (SUVmax) of DbPET were significantly higher than those of WBPET for histological types, excluding lobular carcinoma in situ. The SUVmax of papillary neoplasms was high regardless of low-grade histology and Ki-67 labeling index.ConclusionsDBPET was found to have high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ.     

The distribution of carcinoembryonic antigen in breast carcinoma. Diagnostic and prognostic implications

Carcinoembryonic antigen (CEA) has been shown to be a useful tumor marker in patients with breast carcinoma. The unlabeled antibody immunoperoxidase technique was used to localize CEA in 93 cases of primary breast carcinoma, 15 cases of atypical duct papillomatosis, and 4 cases of duct papilloma. Normal breast epithelium and breast epithelium in fibrocystic disease did not stain positively for CEA. Twenty-four of 27 (88%) intraductal carcinomas, and 47 of 69 (68%) infiltrating duct carcinomas were CEA positive. In contrast, only 5 of 21 (23%) in situ lobular carcinomas and 8 of 24 (33%) infiltrating lobular carcinomas were positive for CEA. All 15 cases of atypical epithelial papillomatosis were negative, whereas 1 of the 4 cases of duct papilloma exhibited microscopic foci of weak CEA positivity. There was a trend for infiltrating duct carcinomas, 3 cm in diameter or smaller, staining strongly positive for CEA, to be associated with synchronous axillary lymph node metastases (P = 0.09). Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region and even from cell to cell. Positive immunohistochemical staining for CEA may play an adjunctive role in discriminating intraductal carcinoma from atypical papillary ductal proliferations.     

Serum sialic acid (TSA/LSA) and carcinoembryonic antigen (CEA) levels in cancer patients undergoing radiotherapy.

The main aim of this study was to evaluate the response of total Sialic Acid (TSA) and "Lipid-bound" Sialic Acid (LSA) compared to Carcinoembryonic Antigen (CEA), in 284 patients undergoing radiotherapy. Serial measurements of TSA by the enzymatic method (Boehringer-Mannheim Kit), LSA by the resorcinol-HC1 (Katopodis and Stock) and CEA by EIA (Abbott Kit) were performed in a total of 1017 blood sera. We statistically estimated the four greater groups of cancer patients [bladder (69), lung (58), uterus (31) and breast (29)]. Diagnostic marker sensitivities (% true positives) estimated from the 0-time-values--before initiation of radiotherapy--in relation to the established cut-off levels were in decreasing order: TSA 89.3% (80 mg/dL). LSA 88.8% (20 mg/dL) and CEA 26.75% (5 ng/mL). The overall tumor marker response to treatment, after its completion, estimated as % of patients with final blood serum levels of these markers, was in decreasing order: LSA 85.6%, TSA 81.3%, and CEA 65.8%. These data show that a) the diagnostic sensitivity of Sialic Acid (LSA/TSA) is more than 3 times higher than that of CEA and b) the response of Sialic Acid (LSA/TSA) to treatment is about 15% higher than that of CEA. In conclusion, this study confirms the high diagnostic sensitivity of Sialic Acid as a tumor marker and suggests that, with marginal superiority of Sialic Acid, all three markers are sufficiently responsive to be employed as adjunctive means in monitoring cancer patients underdoing radiotherapy.     

Carcinomatous meningitis associated with infiltrating lobular carcinoma of the breast

The records of 365 patients with advanced carcinoma of the breast were examined to identify those with CNS involvement. Nineteen (5.2%) developed parenchymal cerebral deposits and 10 (2.7%) developed meningeal infiltration during the course of their disease. Parenchymal cerebral deposits were almost exclusively associated with infiltrating duct carcinoma (95%) and meningeal infiltration (carcinomatous meningitis) was almost exclusively associated with infiltrating lobular carcinoma. Meningeal infiltration occurred late in the course of advanced disease and was associated with diffuse involvement of the bone marrow and abdominal structures.     

Infiltrating lobular carcinoma of the breast: Response to endocrine therapy and survival

The records of 480 patients who received systemic therapy for advanced breast cancer in the University Hospital of South Manchester from 1975 to 1983 were examined. There were 264 with infiltrating duct carcinomas (IDC) and 33 with infiltrating lobular carcinomas (ILC) for whom the response to endocrine therapy was known. There were 92 responses (35%) among the IDC patients and 9 (27%) among the ILC patients. Sixty-seven per cent of IDC patients tested had steroid hormone receptor positive tumours compared to 90% for ILC (P < 0.001). Comparison of survival from diagnosis, disease free interval and survival from relapse showed no significant differences between the two groups. Thus despite almost of ILC patients having hormone receptor positive tumours their survival was similar to that of IDC patients. This appears to be due to a lower than expected response rate to endocrine therapy. This is a further indication of the different biological characteristics of these two histological sub-types of breast carcinoma.     

Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation

Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation. Of the 4 grades of differentiation, the less differentiated Grade III and IV tumors showed significantly lower levels of estrogen and progesterone receptors in infiltrating ductal and lobular carcinoma (P less than 0.001). In contrast, patients with medullary carcinoma had the lowest tissue levels of estrogen and progesterone receptors with approximately 80% of the cases with less than 10 fmol/mg protein. Patients with mucinous carcinoma had the highest percentages of positive estrogen and progesterone receptor levels (75% and 87%, respectively). Sixty-three percent of the patients with Grade IV infiltrating ductal carcinoma were younger than 53 years of age (P less than 0.001). Patients younger than 53 years of age with Grade II and III infiltrating ductal carcinoma also had significantly lower levels of estrogen receptors, but not of progesterone receptors, than those patients older than 53 years of age (P less than 0.001). Nineteen of 20 "normal" breast tissue specimens were negative (less than 3 fmol/mg protein) for estrogen and progesterone receptors. About 50% of 17 tissue specimens from benign breast lesions (fibroadenoma, fibrocystic disease, sclerosing adenosis) showed positive estrogen (greater than 10 fmol/mg protein) or progesterone receptor values. In two patients with gynecomastia, no estrogen or progesterone receptors were detectable.