Assessment of right hepatic artery involvement in patients with biliary tract cancer using color Doppler ultrasonography

Monoclonal antibody (MAb) CC49 binds to human tumour-associated glycoprotein termed TAG-72. CC49 is a second-generation MAb with higher affinity to TAG-72 than the original MAb B72.3. CC49 was applied to 42 samples from different canine mammary tumours, belonging to seven different histopathological types. Immunoreactivity was detected by the use of an avidin-biotin complex immunoperoxidase method. Most sections from all types of mammary neoplasm reacted with this MAb. Normal tissue did not stain or stained only weakly. The results of this study suggest CC49 has selective immunoreactivity for a variety of canine mammary tumours, which seems superior to that reported with MAb 72.3. These results support the proposal for further study of diagnostic and therapeutic uses of CC49 in the management of canine mammary tumours.     

Clinical comparison of radiolocalization of two monoclonal antibodies (mAbs) against the TAG-72 antigen

Ten patients with colorectal cancer metastases received 125I-B72.3 and 131I-CC49 prior to laparotomy (five patients received 1 mg, and five 20 mg of each mAb). Tumor:serum ratios of 131I-CC49 were better than those of 125I-B72.3 (P < 0.01 at 1 mg; P = 0.05 at 20 mg; P < 0.01 at both doses). All known lesions > or = 1 cm in diameter were visualized at the 20 mg dose. There was no difference in absolute tumor uptake of 125I-B72.3 or 131I-CC49. We conclude that mAb CC49 has better relative uptake in colorectal cancers than mAb B72.3.     

Allergic eye disease mechanisms

The histologic distinction between epithelial peritoneal mesothelioma and papillary serous carcinoma diffusely involving the peritoneum may be difficult. Although some investigators have indicated that immunohistochemistry can facilitate this differential diagnosis. only a few studies using a limited number of markers have been published. In this study, the immunoreactivity of keratin 5/6, vimentin, epithelial membrane antigen, thrombomodulin, calretinin, MOC-31, Ber-EP4, carcinoembryonic antigen, TAG-72 (B72.3), CD15 (Leu-M1), placental alkaline phosphatase, CA19-9, CA-125, HBME-1, 44-3A6, and S-100 protein was investigated in 35 epithelial peritoneal mesotheliomas, and 45 papillary serous carcinomas [30 ovarian (10 primary and 20 metastatic to the peritoneum) and 15 papillary serous carcinomas of the peritoneum]. After analyzing the results, it is concluded that calretinin, thrombomodulin, and keratin 5/6 are the best positive markers for differentiating epithelial malignant mesotheliomas from papillary serous carcinomas diffusely involving the peritoneum. The best diagnostic discriminators among the antibodies considered to be negative markers for mesothelioma are MOC-31, B72.3, Ber-EP4, CA19-9, and Leu-M1. Immunostaining for carcinoembryonic antigen, placental alkaline phosphatase, epithelial membrane antigen, vimentin, HBME-1, 44-3A6, CA-125, or S-100 have little or no diagnostic utility in establishing the differential diagnosis between these conditions. The results of this study also confirm previous observations indicating that both papillary serous carcinomas of the peritoneum and serous carcinomas of the ovary have a similar phenotype and, therefore, immunohistochemical studies are not useful in separating these entities.     

Physiologic, biochemical and genetic aspects of malignant hyperthermia

The value of the TAG-72 (CA 72-4) serum marker in primary diagnosis was investigated in 110 patients with histologically diagnosed ovarian cancer. A reference group consisted of 103 patients with benign pelvic masses. Compared to the well-established CA-125, TAG-72 showed a low sensitivity of 42% in the detection of ovarian cancer. By contrast, when the cut-off level for TAG-72 was set at 6 U/ml, it showed a very high specificity of 99%. When the measurement of TAG-72 was combined to that of CA-125, improvements in both the specificity (as compared to a single CA-125 determination) and the sensitivity (as compared to a single TAG-72 assay) were observed. In such a combined assay, our results suggest that the best predictive value (positive and negative) was obtained if CA-125 is assigned a relatively high cut-off value (65 U/ml) in conjunction with a low cut-off level (3.2 U/ml or 4 U/ml) for TAG-72. In the present study, at threshold values of 65 U/ml respectively, a sensitivity of 86%, a specificity of 83% and a positive and negative predictive value of 85% were obtained. In mucinous carcinomas of the ovary, however, the additional TAG-72 determination did not lead to a better predictive power than did CA-125 measurement alone.     

Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer

To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.     

Specificities of anti-sialyl-Tn and anti-Tn monoclonal antibodies generated using novel clustered synthetic glycopeptide epitopes

The fine specificities of MAbs generated using novel synthetic clustered STn and Tn glycopeptides as immunogens were compared with the anti-TAG-72 antibodies B72.3 and CC49. Hapten inhibition experiments demonstrated the specificity of several of the MAbs for STn and Tn expressed on ovine submaxillary mucin and tumor derived MUC-1 mucin. Amongst the STn specific MAbs only the B195.3 MAb shows absolute dependence on the presence of sialic acid and specificity to the simple disaccharide NANAA alpha2-6-GalNAc. Identification of tumor associated carbohydrate epitopes in cluster and monomer configurations are possible using MAbs detecting the defined structure specificities described herein.     

Localization of tumor-reactive lymph node lymphocytes in vivo using radiolabeled monoclonal antibody

BACKGROUND: Lymph node lymphocytes vary in their responsiveness to tumor. A technique has been developed that uses radiolabeled monoclonal antibody (MoAb) against the tumor-associated mucin, TAG-72, and a gamma-detecting probe by which lymph nodes containing microscopic tumor and/or shed TAG-72 can be identified in vivo. The immunologic characteristics of these lymph nodes were examined. METHODS: Patients with colon cancer received 125I-labeled MoAb CC49 by intravenous injection preoperatively. During laparotomy lymph nodes that appeared normal on inspection and palpation but which contained radiolabeled MoAb were identified using a hand-held gamma-detecting probe. These lymph nodes and other lymph node and tumor specimens were resected for analysis. RESULTS: Lymph nodes identified by the probe were found by immunohistochemical studies to contain microscopic tumor and/or shed antigen associated with germinal centers. They were characterized by greater CD4+:CD8+ ratios, rates of expansion, and cytolytic activity compared with lymphocytes from lymph nodes with macroscopic tumor, noninvolved lymph nodes, and tumors. All lymph node lymphocytes identified by the probe demonstrated significant proliferative responses to autologous tumor and, in contrast to lymphocytes from noninvolved lymph nodes, significant proliferative responses to allogeneic TAG-72+ tumor cells and to soluble TAG-72+ mucin. CONCLUSIONS: By locating lymph nodes with microscopic tumor and/or shed antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly identify tumor-reactive lymph node lymphocytes. This technique may be useful in identifying cells for use in adoptive immunotherapy programs and in studying the regulation of immune responses in vivo.     

Construction of phosphorylatable chimeric monoclonal antibody CC49 with a tyrosine srC kinase recognition site

A phosphorylation site for a tyrosine kinase was introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting a synthetic fragment (Tyr) encoding one tyrosine kinase phosphorylation site into an expression vector. The phosphorylation site was created by incorporating the predicted consensus sequences for phosphorylation by the tyrosine kinase at the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified MAb-chCC49 (MAb-chCC49Tyr) was expressed and purified. The MAb-chCC49Tyr protein can be phosphorylated by the tyrosine Src kinase with [gamma-32P]ATP to high radiospecific activity. The 32P-labeled MAb-chCC49Tyr protein binds to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into monoclonal antibodies (MAb) provides a new reagent for the diagnosis and treatment of cancer. This demonstrates that, as was described for the cAMP-dependent protein kinase site, a tyrosine phosphorylation site can also be used to introduce phosphorylation sites into proteins.     

p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.     

Identification of novel membrane structures in Plasmodium falciparum infected erythrocytes

Phosphorylation sites were introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting synthetic fragments encoding two and six phosphorylation sites into an expression vector, pdHL7. The phosphorylation sites were created by using the predicted consensus sequences for phosphorylation by the cAMP-dependent protein kinase to the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified antibodies (MAb-chCC49K1 and MAb-chCC49-6P) were expressed in NS0 cells and purified. The MAb-chCC49K1 protein contains two phosphorylation sites per heavy chain whereas the MAb-chCC49-6P protein contains six sites per heavy chain. Both MAb-chCC49K1 and MAb-chCC49-6P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high specific activity. The 32P-labeled MAb-chCC49K1 and MAb-chCC49-6P proteins bind to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into a monoclonal antibody provides a reagent for the diagnosis and treatment of cancer. The use of multiple phosphorylation sites provides antibodies with very high specific radioactivity and demonstrates that cassettes of phosphorylation sites can be introduced into proteins without altering their functional activity.     

Intraoperative detection of occult colon cancer micrometastases using 125 I-radiolabled monoclonal antibody CC49

BACKGROUND: The detection of locally-disseminated disease is one of the principal goals of oncologic surgery. For this study, a hand-held, gamma-detecting probe was used intraoperatively to assess the extent of colorectal carcinoma in patients previously injected with radiolabeled antibody to the TAG-72 antigen (CC49); this technique is known as Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH). RIGS-positive areas (i.e. those with increased signal over background) have previously been shown to contain carcinoma in a high proportion of cases. However, some RIGS-positive areas had no tumor detectable by clinical examination or routine histopathologic analysis. This study was undertaken to determine if the presence of occult metastases might account for this disparity. METHODS: A total of 57 regional lymph nodes (LN), resected from 16 patients with primary (9) or recurrent (7) colorectal carcinoma, were studied. The patients were injected with 125I labeled CC49 murine monoclonal antibody approximately 3 weeks prior to surgery. After routine histologic evaluation, the LN were analyzed for occult metastases; paraffin sections were cut at 5 levels (50 micron apart) and were examined by histology (hematoxylin and eosin stain [H & E]) and by immunohistochemistry (IHC) with a cocktail of monoclonal antibodies to cytokeratins. RESULTS: Fifty-seven LN were included in this study; 17 were H & E-positive (i.e., contained tumor by routine histologic examination [overt tumor]), while 40 LN were H & E-negative (i.e., no evidence of tumor after routine histologic examination). Thirty-nine LN were RIGS-positive, but only 14 of these were H & E-positive. Of the 25 RIGS-positive/H & E-negative LN, 10 (40%) demonstrated the presence of occult metastases after serial section/IHC analysis. Thus, a total of 27 LN contained metastatic carcinoma (17 overt, 10 occult); routine histologic analysis was able to identify tumor in only 17 of these 27 LN (63%), while the probe signaled the presence of tumor in 24 of these LN (89%). None of the RIGS-negative/H & E-negative LN were found to have occult metastases (0/15). Specific immunoreactivity with CC49 antibody was observed in 5 of 15 RIGS-positive/H & E-negative LN in which no tumor could be identified by any method (histopathology or IHC. CC49 immunoreactivity was not observed in 15 RIGS-negative/H & E-negative LN. CONCLUSIONS: The finding of a RIGS-positive LN had a significant association with the presence of tumor cells (P < 0.05). In this study, the RIGS procedure was more sensitive than clinical or histopathologic examination in detecting the regional spread of a tumor. Furthermore, in LN that showed no evidence of tumor by routine histopathologic examination, a positive RIGS reading was significantly associated with the presence of occult LN metastases (P < 0.01). This study is the first to demonstrate the detection of histologically occult tumor by a remote imaging device. RIGS assessment is a highly sensitive method for detecting occult tumor deposits, and may guide therapeutic intervention in patients with colorectal carcinoma.     

Inhibin immunohistochemistry applied to ovarian neoplasms: a novel, effective, diagnostic tool

Immunohistochemistry using monoclonal antibodies against human inhibin, a peptide hormone produced by ovarian granulosa cells to inhibit follicle-stimulating hormone (FSH), has been recently applied to diagnostic anatomic pathology. This investigation hypothesizes that inhibin immunohistochemistry will aid in the crucial clinical distinction between sex cord-stromal and other primary ovarian neoplasms. Available H&E slides and clinical information from a retrospective surgical series of 186 primary ovarian tumors were reviewed to verify diagnoses, and representative paraffin sections were immunostained with anti-inhibin (R1 monoclonal, Serotec, Kidlington, Oxford, UK). Immunoreactivity was graded as weak/strong (W/S), and the proportion of strong staining cells was coded as follows: S1 = <10%, S2 = 10%-50%, S3 = >50%, respectively. Inhibin immunoreactivity for 137 sex cord-stromal lesions was as follows: 100% of 66 granulosa cell tumors: 80% S3, 20% S2; 100% of 17 Sertoli-stromal tumors: 90% S3, 10% S2; 100% of 13 hyperplastic follicular/stromal lesions: 90% S3, 10% S2; 100% of six steroid cell tumors: 100% S3; 90% of 18 thecomas: 40% S3, 10% S2, 10% S1, 30% W; 0% of 12 fibromas, three myxomas, and two sclerosing stromal tumors. None (0 of 49) of the other ovarian neoplasms exhibited inhibin: 22 carcinomas, 12 carcinosarcomas, seven small cell carcinomas, six germ cell tumors, and two lymphomas. In the typical case, the distinction between sex cord-stromal and other ovarian neoplasms requires nothing more than routine pathological examination. In diagnostically challenging cases, our data indicate that inhibin immunohistochemistry is a very useful adjunct because granulosa and sertoli-stromal tumors are positive whereas other potential mimickers have been negative thus far.     

T cell targeting of TAG72+ tumor cells by a chimeric receptor with antibody-like specificity for a carbohydrate epitope

BACKGROUND & AIMS: Chimeric receptors with specificity for defined tumor antigens are valuable tools for targeting cytolytic T cells specifically to tumor cells. The aim of this study, for the situation of gastrointestinal cancer, was to investigate the generation of a chimeric T cell receptor that specifically binds the tumor antigen TAG72 (CA72-4) and transmits a signal for cellular activation. METHODS: A single-chain antibody (scFv) was derived from the monoclonal anti-TAG72 antibody B72.3 by phage display techniques (B72.3-scFv) and fused to the signaling unit of the Fc epsilon-RI receptor gamma chain, resulting in a chimeric signaling receptor, B72.3-scFv-gamma. RESULTS: The B72.3-scFv and the chimeric B72.3-scFv-gamma receptor bound specifically to the TAG72 antigen. After transfection, T cells expressing the chimeric B72.3-scFv-gamma specifically recognized TAG72 positive cells. Cross-linking of the chimeric receptor with antigen resulted in interleukin 2 release and cytolytic activity against TAG72 positive tumor cells in vitro. CONCLUSIONS: T cells equipped with the chimeric anti-TAG72 receptor can be specifically activated to target and lyse TAG72 positive gastrointestinal tumor cells.     

Phase II study of dual 131I-labeled monoclonal antibody therapy with interferon in patients with metastatic colorectal cancer

The combination of COL-1 (anti-CEA) and CC49 (anti-TAG-72) has shown an increase in binding and distribution in colon cancer by immunoperoxidase staining compared to either antibody alone. To overcome tumor heterogeneity and allow delivery of higher radiation dose, 131I-labeled COL-1 and CC49 at a total dose of 75 mCi/m2 (2775 MBq/m2) were simultaneously administered to 14 patients with metastatic colon cancer. alpha-IFN (3 x 10(6) IU) was given s.c. on days -5 to +3 to increase carcinoembryonic antigen and TAG-72 antigen expression. Most patients had mild symptoms during IFN therapy, including mild neutropenia, fever, and malaise, which rapidly subsided after IFN cessation. No acute allergic reactions occurred with radioimmunotherapy; two patients experienced transient, delayed grade 2 arthralgias. Transient neutropenia and/or thrombocytopenia, which was maximal at 4-6 weeks, were consistent side effects without adverse events. All patients had tumor localization, and 13 of 14 patients achieved 4+ (highest grade) localization readings to at least one known site of disease. No objective responses occurred; 4 patients were stable and 10 progressed. Tumor dose estimates varied from 393 to 1327 cGy, including liver and extrahepatic sites. Combining two complementary antibodies and IFN administration appeared to increase localization intensity and radiation doses at tumor sites as compared to historical controls. The amount of radiation delivered to tumor sites was still below that required to cause tumor regressions in metastatic colorectal cancer.     

The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells

OBJECTIVE: To examine the usefulness of clinical stage, tumour differentiation and prostate-specific antigen (PSA) level, alone and in combination, to predict regional nodal metastases in individual patients with localized prostate cancer. PATIENTS AND METHODS: The usefulness of digital rectal examination (DRE), biopsy Gleason sum and PSA, alone and in combination, to predict nodal metastases in an individual patient was examined. The study included 689 patients who had laparoscopic or open pelvic lymph node dissection for clinical stage T1-3 prostate cancer. The Kruskal-Wallis test, Mantel-Haenszel test, chi-squared test and logistic regression were used for continuous, ordinal, categorical, and multivariate analysis, respectively. RESULTS: Of the 689 patients who underwent radical prostatectomy, 52 (8%) had nodal metastases. Although clinical stage, DRE, pre-operative PSA level and biopsy Gleason sum were significantly related in the univariate analysis, only pre-operative PSA level and biopsy Gleason sum were significant predictors of lymph node status in a multivariate analysis. However, based on a receiver operating characteristic curve, a model with satisfactory sensitivity and specificity could not be obtained. CONCLUSION: Current estimations of primary prostate cancer biology using pre-operative PSA level, clinical stage and biopsy Gleason sum are not sufficiently sensitive to predict nodal metastases, and pelvic lymphadenectomy remains the definitive method of detection.     

Xenopus laevis fertilisation: analysis of sperm motility in egg jelly using video light microscopy

OBJECTIVE: To evaluate the origin of pseudomyxoma peritonei (PMP) in Chinese women. METHODS: The clinicopathologic features of 15 cases of PMP were reviewed. Immunostaining using antibodies for CK7 and CK20 was performed in the ovarian, appendiceal and peritoneal lesions of these cases. RESULTS: Appendiceal pathology was documented in five cases, including four mucinous cystadenoma and one simple mucocele. Eight ovarian tumors were found, including seven mucinous cystadenocarcinomas of low malignant potential and one mucinous cystadenoma. Synchronous ovarian and appendiceal lesions were discovered in three cases. One patient had adenocarcinoma of the pancreas. The origin of mucin production was not known in four cases with metastatic adenocarcinoma found in two of them. Immunoreactivity for CK20 was demonstrated in the tissues derived from the peritoneum, ovary, appendix and pancreas while only 23% (3 out of 13 women) of the peritoneal lesions and 33% (2 out of 6 women) of the ovarian tumors were immunoreactive for CK7. CONCLUSIONS: PMP is a heterogeneous lesion, which may develop from mucinous metaplasia of the peritoneum or from appendiceal, or ovarian lesions. Careful examination of the ovary and appendix with performance of appendectomy is advised in every case of PMP. Immunohistochemical examination of the peritoneal, ovarian or appendiceal lesions using antibodies, in particular that for CK7 would help in defining the origin of mucin production.     

Phase I study of intravenous Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma

CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-aminophenyl) propyl)-tris-4,7,10- ((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu. Preclinical studies had shown that Lu-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-labeled CC49. The starting dose of Lu was 10 mCi/m2 given i.v. with the dose of CC49 held constant at 20 mg. Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks. The dose of radioactive Lu was escalated by 15 mCi/m2 for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m2 Lu; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES). Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu based on imaging and biopsy data. Analysis of bone marrow biopsies demonstrated that most of the Lu was localized in the cellular compartment and not in the bone. No antitumor responses were observed. Intravenous administration of 15 mCi/m2 Lu-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose. However, prolonged retention of Lu in the RES, including the bone marrow, was observed and limited the dose of Lu that could be given. Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate.     

Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia

BACKGROUND: Radioimmunoguided surgery (RIGS) by means of radiolabeled monoclonal antibodies and a probe has been reported to be useful in recognizing subclinical tumor deposits during operation. Aim of this study was to understand the limits of this technique and to assess the potential diagnostic use of RIGS in colorectal cancer surgery. METHODS: Monoclonal antibody B72.3 reacting with TAG 72 antigen, labeled with iodine 125, was injected in 32 patients with primary tumors and in 22 patients with recurrent colorectal cancer. One hundred thirty-three suspected tumor sites were evaluated during operation by means of probe and resected with immunohistochemistry as control. RESULTS: Primary tumor sites were localized by RIGS in 60% of cases, and recurrent sites were localized in 82% of cases. There was a significant correlation both for primary (p < 0.001) and recurrent (p < 0.001) tumor sites between intraoperative RIGS findings and TAG 72 tumor antigen expression. Results obtained with the probe were instrumental in modifying the surgical approach in six (27%) of 22 patients with recurrences, allowing the removal of tumor masses that would otherwise have been overlooked. CONCLUSIONS: The results of RIGS seems to be encouraging in terms of clinical use. The potential high diagnostic resolution appears to improve surgical ablation of colorectal cancer, especially in patients with recurrent cancer or suspected recurrent tumors who have negative results for intraabdominal disease by all other roentgenographic criteria with rising carcinoembryonic antigen or TAG 72 antigen levels.     

The establishment of a radioactive waste disposal facility in Western Australia for low level waste

Core needle biopsies (CNB) are often used for the diagnosis of breast lesions. In some breast cancer patients, e.g., those treated with preoperative chemotherapy, the CNB specimen might be the only pretreatment tissue sample available for studies of prognostic and predictive markers. Our purpose was to evaluate whether marker studies performed on CNB specimens accurately reflect the marker status of the tumor. Immunostaining for five commonly used prognostic and predictive markers was performed on both CNB and subsequent excision specimens from 56 consecutive patients who had a CNB with carcinoma followed by excision of the tumor. None of the patients received radiotherapy or chemotherapy between the CNB and the excision. Paraffin sections of the CNB and excision specimens were immunostained for bcl-2, estrogen receptor (ER), c-erbB-2, and p53. These markers were scored as positive or negative. Microvessel density (MVD) was scored as a continuous variable on sections immunostained for Factor VIII-related antigen by calculating the average number of microvessels in three 224x fields of highest tumor vascularity ("hot spots"). Immunostaining results for bcl-2, ER, c-erbB-2, and p53 on the CNB and the corresponding excision specimens were 100% concordant. Although there was significant correlation between MVD on the CNB specimens and the corresponding excisions (r = 0.507, P = 0.0002), the mean MVD on the CNB and corresponding excision specimens differed by more than 10% in 85.7% of cases, with differences ranging from 4.3 to 233.3%. MVD was higher in the CNB than in the excision specimens in 30 (61.2%) of 49 cases. In conclusion, in all of the cases studied, accurate results for the dichotomously scored markers bcl-2, ER, c-erbB-2, and p53 were obtained on CNB specimens. In contrast, in most cases, MVD, which was scored as a continuous variable, could not be reliably assessed on the CNB specimen.     

Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors

Neural cell adhesion molecules (NCAM) represent specific markers of neuroendocrine (NE) differentiation in lung cancer. Because the polysialic acid form (NCAM-PSA) has reduced adhesion properties, we hypothesized that NCAM-PSA expression could favor metastatic spread. Immunostaining of NCAM and NCAM-PSA were therefore compared in 120 NE lung tumors, including 17 typical carcinoids, 3 atypical carcinoids, 30 large cell NE carcinomas and 70 small cell lung carcinomas, as compared with 25 adenocarcinomas and 25 squamous cell carcinomas. Neural cell adhesion molecules were negative in adenocarcinomas and squamous cell carcinomas but were constantly expressed in all NE tumors from typical carcinoids to small cell lung carcinomas. NCAM-PSA expression was significantly more frequent in high-grade tumors, with 24 of 30 positive cases in large cell NE carcinomas and 65 of 70 positive cases in small cell lung carcinoma, than in carcinoids with 10 of 17 and 2 of 3 positive cases in typical carcinoids and atypical carcinoids, respectively. The neural cell adhesion molecule-polysialic acid form scores of staining were significantly higher in high-grade as compared with low-grade tumors (p = 0.002), and were correlated with nodal spread (p = 0.04) and metastasis (p = 0.016) across histologic classes but not in individual tumor type. We conclude that NCAM-PSA connotes poor differentiation and aggressive clinical behavior in the spectrum of NE lung tumors, but cannot be regarded as a prognostic factor in individual tumor classes.