Effects of progesterone therapy on serum sclerostin levels in healthy menopausal women: a 3-month randomized, placebo-controlled clinical trial.

Sclerostin, a natural hormone made in bone, suppresses bone formation. Sclerostin is also decreased by estrogen. Progesterone, estrogen's menstrual partner, stimulates bone formation. It is unclear whether progesterone influences sclerostin. This study showed that progesterone did not change sclerostin using serum remaining from a randomized progesterone hot flush therapy trial. INTRODUCTION: Progesterone and sclerostin are both endogenous hormones acting through osteoblast-origin cells and promote or suppress bone formation, respectively. Estradiol suppresses sclerostin, but progesterone, its menstrual cycle partner hormone, has unclear sclerostin relationships. We postulated that progesterone therapy would influence serum sclerostin levels. METHODS: We obtained sclerostin levels for an ethics-approved post hoc analysis. Fasting sclerostin was measured in all remaining sera from a previous 12-week randomized controlled trial (RCT) of oral micronized progesterone (progesterone) for menopausal (> 1 year after last flow) vasomotor symptoms (VMS). Women in the RCT took 300 mg progesterone at bedtime or placebo (1:1) in a trial showing progesterone significantly decreased VMS. RESULTS: Participants were healthy menopausal, primarily Caucasian (91.2%) community-dwelling women (± SD), 55.2 ± 4.6 years old with BMI 24.9 ± 2.9 kg/m2. The baseline sclerostin level in 60 women was 28.41 ± 10.47 pmol/L. Baseline sclerostin was not correlated with the run-in VMS score (r = 0.143, P = 0.294). Paired baseline and 12-week RCT data for 52 women showed serum sclerostin levels did not change related to experimental therapy (P = 0.504). Changes in final sclerostin values adjusted for baseline were progesterone (- 1.07 ± 7.96 pmol/L) and placebo (- 2.64 ± 8.70 pmol/L). In observational data (n = 60), baseline sclerostin levels correlated with the General Framingham Cardiovascular (CVD) Risk score (r = - 0.398, P = 0.003) and self-reported health by SF-36 quality of life instrument (QoL, r = - 0.331, P = 0.016). CONCLUSION: Physiological oral micronized progesterone did not stimulate nor suppress serum sclerostin levels based on post hoc analysis of RCT data. Exploratory results, however, showed sclerostin negatively correlated with CVD risk and QoL. ClinicalTrials.gov #NCT0146469.

Progesterone therapy increases free thyroxine levels--data from a randomized placebo-controlled 12-week hot flush trial.

OBJECTIVE: Thyroid hormones and progesterone both influence core temperature, metabolism and are crucial during pregnancy. Our objective was to discover whether progesterone therapy caused changes in thyroid physiology compared with placebo. DESIGN: Post hoc analysis from a randomized (1:1) placebo-controlled 12-week trial of oral micronized progesterone (Progesterone, 300 mg/d at bedtime) for hot flushes (vasomotor symptoms, VMS) conducted in an academic medical centre. PATIENTS: Postmenopausal euthyroid, healthy (without cardiovascular diseases or risks) women, 1-11 years since last flow on no thyroid or ovarian hormone therapy with VMS participated. MEASUREMENTS: Primary outcomes were final and 12-week changes in TSH, FreeT3 and FreeT4 on progesterone vs placebo. RESULTS: Women with thyroid data (69 of 133 in original trial) were randomized to progesterone (n = 39) or placebo (n = 30)-baseline thyroid values were normal. There were no VMS-thyroid interactions-VMS Score (number × intensity) did not correlate with TSH, FreeT3 or FreeT4 (Spearman's rank correlations: -0.03 to -0.19, respectively; all P > 0.15). At 12 weeks on progesterone, TSH levels tended to be lower (1.7 mU) than on placebo (2.2), P = 0.06; FreeT4 levels were higher (16.4 pmol/l) than on placebo (15.3), P = 0.02. FreeT3 was unchanged throughout. Analysis of covariance showed a significant increase in FreeT4 on progesterone (+2.5 pmol/l; 1.9-3.0) vs on placebo (+1.7; 1.1-2.4) with 95% CI of difference = 0.8 pmol/l [0.0, 1.6], P = 0.04. CONCLUSIONS: Progesterone caused a significant FreeT4 increase that was discovered during this randomized controlled VMS trial. The clinical importance of this increased FreeT4 level remains to be documented. Registered at ClinialTrials.gov#NCT00152438.

Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: an analysis of p16/MTS1 tumor suppressor gene inactivation.

Neoplasms of the endocrine pancreas are extremely rare, and molecular mechanisms influencing their development are poorly understood. Nevertheless, gastrinomas have become a paradigm for the study of hormonally active tumors. In the present study, 12 gastrinoma and nonfunctioning pancreatic neuroendocrine tumor specimens were evaluated for genetic alterations of the p16/MTS1 tumor suppressor gene. DNA extracted from microdissected portions of paraffin-embedded tumor sections were examined for mutations and homozygous deletions using "Cold" single-strand conformation polymorphism and semiquantitative PCR-based analyses, respectively. Samples were also analyzed for the presence of 5' CpG island hypermethylation using methylation-specific PCR. The p16/MTS1 gene was found to be homozygously deleted in 41.7% of tumors and methylated in 58.3%, but no mutations were identified by single-strand conformation polymorphism analyses. Overall, 91.7% of the specimens demonstrated inactivating alterations in p16/MTS1. These data suggest that transcriptional silencing of p16/MTS1 is a frequent event in these rare and poorly understood tumors.

Premenopausal Trabecular Bone Loss is Associated with a Family History of Fragility Fracture.

INTRODUCTION: Although a fragility fracture family history (FFFH+) has repeatedly been shown to be associated with lower bone mineral density (BMD), its relationship to human BMD change is unclear. Animal research, however, documented that different purebred strains within rodent species have wide ranges in rates of bone acquisition during growth as well as in change post-ovariectomy. Our objective was to compare the rate of premenopausal spinal trabecular BMD change between women with and without a general family history of fragility fracture. PARTICIPANTS AND METHODS: Healthy premenopausal community women participated in prospective observational studies at two academic medical research centres: Vancouver, Canada (n = 66) and Munich, Germany (n = 20). The primary outcome was annual spinal BMD change, measured by quantitative computed tomography (QCT). The two studies employed similar methodologies for assessing QCT and FFFH. RESULTS: Volunteer community participants had a mean age of 36.0 (SD, 6.9) years, body mass index 22.5 (2.4) and baseline QCT of 150.2 (22.5) mg/cm3 trabecular bone. The rates of BMD change were similar in both cities: - 3.5 (5.1)/year Vancouver, - 2.0 (3.4)/year Munich (95 % CI of difference: - 3.9, 0.9). Over a third of the women (31 of the 86, 36 %) reported FFFH+. Those with and without a FFFH were similar in demographics, nutrition, exercise, menstrual cycle and luteal phase lengths and physiological measures (serum calcium, osteocalcin and estradiol). However, women with FFFH+ lost trabecular BMD more rapidly: FFFH+, - 4.9 (5.0), FFFH-, - 2.2 (4.4) mg/cm3/year (95 % CI diff - 0.7 to - 4.8, F1.83 = 7.88, p = 0.006). FFFH+ explained 7.7 % of the variance in QCT volumetric trabecular spinal bone change/year in these healthy premenopausal women. CONCLUSION: This study shows for the first time that having a history of a fragility fracture in a family member is associated with a greater rate of premenopausal spinal trabecular bone loss.

Lymphocyte subsets and activation in prediabetes.

Peripheral blood lymphocytes were obtained from 65 individuals: 34 nondiabetic patients with islet cell autoantibodies (ICA) (prediabetic phase), 9 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM), 6 ICA-negative siblings or offsprings of IDDM patients, and 16 ICA-negative controls. The presence of lymphocyte abnormalities and/or activation was examined with dual fluorescence flow cytometry. The percentages of B cells, total T-lymphocyte, and helper T-lymphocyte (Th) and cytotoxic/suppressor T-lymphocyte (Tc/s) subsets and their ratio were not significantly different among the patient groups. No increased expression of interleukin 2 receptor on T-lymphocyte was found in newly diagnosed IDDM or prediabetic individuals. Sixteen of 49 patients had significantly increased number of T-lymphocyte expressing HLA-DR. A significant increase in the number of both Th and Tc/s subsets expressing HLA-DR was found in only 3 of 16 patients. This increase was unrelated to the patients's relative ICA titer or HLA-DR phenotype. On the other hand, the relative density of the DR antigen (RAD-DR) was significantly increased on both Th (886 +/- 120) and Tc/s (1250 +/- 273) in 13 of 38 patients compared with control patients (Th 484 +/- 129 and Tc/s 460 +/- 166). The RAD-DR on Tc/s correlated with the relative ICA titer and was greatest on DR3/4-phenotyped T-lymphocytes. In addition, significantly increased RAD-DR was found in noncontrol patients with impaired insulin release responses at 1 and 3 min to intravenous glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Ex vivo electrical impedance measurements on excised hepatic tissue from human patients with metastatic colorectal cancer.

Point-wise ex vivo electrical impedance spectroscopy measurements were conducted on excised hepatic tissue from human patients with metastatic colorectal cancer using a linear four-electrode impedance probe. This study of 132 measurements from 10 colorectal cancer patients, the largest to date, reports that the equivalent electrical conductivity for tumor tissue is significantly higher than normal tissue (p < 0.01), ranging from 2-5 times greater over the measured frequency range of 100 Hz-1 MHz. Difference in tissue electrical permittivity is also found to be statistically significant across most frequencies. Furthermore, the complex impedance is also reported for both normal and tumor tissue. Consistent with trends for tissue electrical conductivity, normal tissue has a significantly higher impedance than tumor tissue (p < 0.01), as well as a higher net capacitive phase shift (33° for normal liver tissue in contrast to 10° for tumor tissue).

Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis.

Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize; they have been called metastasizing mixed tumor (MZMT) of salivary glands. We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At the time of discovery of metastatic disease, the patients, six women and five men, ranged in age from 20 to 83 years. Primary sites of involvement included the parotid gland (eight cases), submandibular gland (two cases), and the nasal septum (one case). With one exception, all the patients had at least a single recurrences of their primary mixed tumor, but two or more recurrences were the norm before development of metastatic foci. The metastases were discovered from six to 52 years following the occurrence of the primary tumor. Metastatic deposits were identified in bone, lung, regional lymph nodes, skin, kidney, retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The metastases either occurred simultaneously with an episode of recurrent mixed tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of the primary, recurrent, and metastatic neoplasms was surgical excision. Follow-up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed seven patients to be alive without disease (64%) and two dead of causes unrelated to metastatic disease (18%). Two patients (18%) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two of the cases. DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors. Retrospective analysis of histologic parameters (mitotic rate, cellular pleomorphism, infiltrative growth, vascular or lymphatic invasion) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms.

Melanotic neuroectodermal tumor of infancy. Clinicopathological, immunohistochemical, and flow cytometric study.

Twenty cases of melanotic neuroectodermal tumor of infancy (MNTI) are reported. The patients (13 females, seven males), whose ages ranged from 1 to 9 months (mean, 5 months), typically presented with a rapidly growing mass. Tumor sites included the maxilla (13 cases), mandible (three cases), dura (two cases), brain (one case), and skull/orbit (one case). The mean tumor size was 3.5 cm (range, 1.0-10.0 cm). Follow-up was obtained on 12 cases. Five tumors (45%) recurred within 4 months of diagnosis, but none metastasized. One surgical death occurred. Histologic appearance was distinctive, with tubular or alveolar formations of large melanin-containing cells around nests of smaller neuroblastic cells possessing scant or fibrillar cytoplasm. Twelve tumors were studied immunohistochemically; tumor was positive for cytokeratin in 12 of 12, for HMB 45 in 12 of 12, for vimentin in seven of eight, and for epithelial membrane antigen (EMA) in four of nine tumors, mainly in the large cells. Neuron-specific enolase (NSE) (seven of 12) and Leu 7 (nine of 12) were positive in small and large cells; some tumors also expressed synaptophysin (four of 12), glial fibrillary acidic protein (GFAP, three of 12 tumors), or S-100 protein (two of 12 tumors). No staining was found for chromogranin, desmin, or carcinoembryonic antigen (CEA). Eight of 10 tumors studied had interpretable results on flow cytometry (FCM) (four DNA diploid, three DNA aneuploid, and one DNA diploid with a prominent shoulder). Tumor recurred locally in two of five cases with follow-up, and we were unable to demonstrate the usefulness of FCM in predicting recurrences. Further studies are necessary to define better the potential usefulness of FCM in predicting aggressive behavior. Distinctive morphology and multiphenotypic (epithelial, neural, melanocytic) expression distinguish MNTI from melanoma and metastatic neuroblastoma.

Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases.

Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.

DNA analysis of cardiac myxomas: flow cytometry and image analysis.

Cardiac myxoma is the most common primary tumor of heart, but there is a longstanding controversy over whether it is a true neoplasm or a reactive lesion. We analyzed 24 cardiac myxomas from 22 patients: 22 by DNA flow cytometry and five by image analysis. Two myxomas were aneuploid; one of those analyzed by flow cytometry, and the other by image analysis. Proliferative fractions (S + G2/M) were high in three tumors from patients with multiple myxomas (mean, 15.9%; SD, 4.0%) as compared with 12 solitary uncomplicated myxomas (mean, 7.7%; SD, 6.0%). S-phase and proliferative fractions were low in embolic, recurrent, and solitary myxomas. The presence of aneuploidy in some myxomas supports a neoplastic origin for this tumor.

Diagnostic considerations in molar gestations.

Hydatidiform moles (HMs) are classified as partial or complete based on a combination of gross, histologic, and karyotypic features. Adherence to strict and reproducible diagnostic criteria is needed to ensure accurate diagnosis and minimize interpathologist variability. Using the kappa statistic as a measure of agreement, the morphologic, flow cytometric, and clinical features of 80 cases of HM or suspected HM were analyzed sequentially by three pathologists to evaluate intrapathologist and interpathologist variability. Poor interpathologist agreement was obtained when histology alone was used for diagnosis. The combination of gross morphology and histology resulted in poor to good agreement. Good interpathologist agreement was obtained, however, when objective data (DNA content determined by flow cytometry) were included in the analysis. Our data indicate that pathologist concordance is maximized when the diagnosis is based on a combination of morphology and DNA content.

Flow cytometric analysis of endometrial stromal sarcoma.

Twenty-two endometrial stromal sarcomas were studied by flow cytometric analysis and the results were correlated with surgical stage, nuclear grade, mitotic index, and recurrence. Ploidy determination was not helpful in predicting recurrence in patients with Stage I disease because all 14 were diploid. Only 2 of the 22 tumors were aneuploid; both were high-stage neoplasms. Cell proliferation (%S or %S + %G2/M) did not significantly correlate with vascular invasion, nuclear grade, mitotic index, or surgical stage. Of the 13 Stage I neoplasms with follow-up data, three recurred. The mean proliferation index (%S + %G2/M) of those that recurred was 12.81 +/- 0.47, which did not differ from those that did not recur (mean 12.25 +/- 4.11).

Heterophilic antibodies produce spuriously elevated concentrations of the MB isoenzyme of creatine kinase in a selected patient population.

Dual-site murine antibody-based immunoassays are commonly used in clinical laboratories to quantitate the MB isoenzyme of creatine kinase (CK-MB). Because the serum level of CK-MB is a relatively specific and sensitive indicator of myocardial ischemic damage, accurate quantitation is essential for a correct diagnosis. Heterophile antibodies (eg, human anti-murine antibodies) can interfere with these assays, however, and produce erroneous results. A subpopulation of 19 surgical patients with colorectal carcinoma who had received injections of an 125I-labeled murine monoclonal antibody directed against a tumor-associated glycoprotein was studied. Serum specimens from eight patients (42%) showed a marked increase in the level of CK-MB and normal total CK concentrations. The increased concentrations of CK-MB, which were attributed to interference by human antimurine antibodies, were substantially reduced in these specimens after a heterophile blocking reagent was added. However, this reagent did not significantly alter the serum level of CK-MB in patients who had clinical evidence of acute myocardial ischemia.

Vacuum-assisted stereotactic breast biopsy: histologic underestimation of malignant lesions.

HYPOTHESIS: The histopathologic correlation between stereotactic core needle biopsy and subsequent surgical excision of mammographically detected nonpalpable breast abnormalities is improved with a larger-core (11-gauge) device. DESIGN: Retrospective medical record and histopathologic review. SETTING: University-based academic practice setting. PATIENTS: Two hundred one patients who underwent surgical excision of mammographic abnormalities that had undergone biopsy with an 11-gauge vacuum-assisted stereotactic core biopsy device. MAIN OUTCOME MEASURE: Correlation between stereotactic biopsy histologic results and the histologic results of subsequent surgical specimens. RESULTS: Results of stereotactic biopsy performed on 851 patients revealed atypical hyperplasia in 46 lesions, ductal carcinoma in situ (DCIS) in 89 lesions, and invasive cancer in 73 mammographic abnormalities. Subsequent surgical excision of the 46 atypical lesions revealed 2 cases of DCIS (4.3%) and 4 cases of invasive carcinoma (8.7%). Lesions diagnosed as DCIS on stereotactic biopsy proved to be invasive carcinoma in 10 (11.2%) of 89 patients on subsequent excision. Stereotactic biopsy completely removed 21 (23.6%) of 89 DCIS lesions and 20 (27.4%) of 73 invasive carcinomas. CONCLUSIONS: In summary, 11-gauge vacuum-assisted core breast biopsy accurately predicts the degree of disease in the majority of malignant lesions; however, understaging still occurs in 11% to 13% of lesions showing atypical hyperplasia or DCIS.

Ascorbic acid-dehydroascorbate induces cell cycle arrest at G2/M DNA damage checkpoint during oxidative stress.

Reactive oxygen species induce cellular damage and have been implicated as mediators for cellular signaling pathways. However, a linkage between the cellular redox status and cell cycle progression has not been demonstrated. We previously demonstrated, using the Chinese hamster ovary cell line AS52, that the cytotoxic and mutagenic effects of oxidative stress is prevented by ascorbic acid (AA), but only when cells are treated with AA prior to treatment with the stressor. To elucidate the mechanism(s) responsible for this effect, we determined the effect of AA on cell cycle progression during oxidative stress. Flow cytometric analyses demonstrated that treatment of AS52 cells with AA (50 microM), prior to treatment with a radical generating system (RGS), enhanced cell cycle arrest at the G2/M DNA damage checkpoint when compared to cells treated with RGS. AA had no effect on cell cycle progression in the absence of oxidative stress. Furthermore, under conditions that prevent the reduction of dehydroascorbate (DHA), the oxidized form of AA, cell cycle arrest was also induced at the G2/M DNA damage checkpoint. These observations demonstrate that during periods of oxidative stress, AA functions as an antioxidant and DHA enhances transient arrest at the G2/M checkpoint by delaying the activation of cyclin B-cdc2. These results suggest the presence of a unique redox mechanism for the regulation of cell cycle progression and also demonstrate a novel mechanism by which AA protects cells from damage due to oxidative stress.

Antimutagenic and promutagenic activity of ascorbic acid during oxidative stress.

Ascorbic acid (AA) has both antioxidant and prooxidant activities. However, there have not been any studies to elucidate the molecular mechanisms that determine whether AA functions as an anti- or a prooxidant during oxidative stress. The results of this study, using the Chinese hamster ovary cell line AS52 as a model system, demonstrate that there is a temporal relationship between the anti- and prooxidant activities of a physiologically relevant concentration of AA (50 microM) and oxidative stress. Treatment of cells with AA (50 microM) 24 hr prior to treatment of the cells with a radical generating system (RGS) results in a statistically significant inhibition of the cytotoxicity and mutagenicity associated with exposure of AS52 cells to oxidative stress. Conversely, cotreatment of cells with AA and the RGS results in a statistically significant increase in both the cytotoxic and mutagenic effects of oxidative stress when compared to cell populations exposed only to the RGS. The results, using a novel histochemical-computer image analysis system to detect hydrogen peroxide (H2O2), also demonstrate that there is a direct correlation between the ability of AA to decrease the levels of H2O2 in cells and the cytotoxic and mutagenic effects of oxidative stress. This study suggests that the time at which AA is administered in relation to exposure to oxidative stress has an impact on AA antimutagenic activity, and this may explain the conflicting results concerning the effectiveness of AA as a cancer chemopreventive agent.

Localization of monoclonal antibody CC49 in colonic metastasis from renal cell carcinoma.

We report a rare case of solitary metastasis from renal cell carcinoma which manifested as a primary colonic tumour 5 years after nephrectomy. A monoclonal antibody CC49 (anti-TAG-72 antibody), used in Radioimmunoguided Surgery, was found to localize in the tumour. Pathological examination revealed metastasis of renal cell carcinoma in the colon. Immunohistochemistry with CC49 showed moderate staining of the colonic mucosa around the metastasis with no reaction in the tumour itself. Based on this case and other published studies, we conclude that TAG-72, the antigen manifested in many adenocarcinomas, can be up-regulated and expressed in normal colonic mucosa adjacent to another tumour as a result of stimulations, such as cytokine release, in response to this tumour.

Autoradiographic evaluation of radiolabeled monoclonal antibody B72.3 distribution in tumor and lymph nodes of adenocarcinoma patients.

Monoclonal antibody B72.3 recognizes a pancarcinoma antigen termed TAG-72 and is the MAb in "OncoScint CR/OV". Patients undergoing surgical resection of primary or metastatic colorectal or breast carcinoma or pseudomyxoma peritonei were injected i.v. with 125I-labeled MAb B72.3. Autoradiography identified the tissue distribution of the injected radiolabeled MAb B72.3. Immunohistochemical staining identified the corresponding spatial distribution of the target antigen, TAG-72. The labeling pattern seen using autoradiography closely matched the pattern that was observed using immunohistochemical techniques. This was especially notable in the mucin-containing compartments of the different tumors. The 125I-B72.3 was also found associated with the neoplastic cells, demonstrating a good penetration and specificity of the radiopharmaceutical through the tumor masses. The regional lymph nodes examined were the only tissues in which autoradiography and immunoperoxidase gave different results. In these specimens, the presence of TAG-72 antigen in the parafollicular area, as shown by immunoperoxidase, contrasted with the silver grain deposition, due to the 125I-B72.3, in germinal centers. These findings suggest differences in the clearance pathways of the TAG-72 antigen and B72.3 MAb.

Radioimmunoguided surgery in primary colorectal carcinoma: an intraoperative prognostic tool and adjuvant to traditional staging.

BACKGROUND: The prognostic value of traditional staging classification for colorectal cancer has changed little since Dukes created the first staging scheme. Some patients with known metastatic disease are long-term survivors, while other patients with local disease die early. New intraoperative cancer detection technology, the radioimmunoguided surgery (RIGS) system, is being studied as a tool to aid in prediction of patient outcome. PATIENTS AND METHODS: Thirty-one patients with primary colorectal cancer were injected with the monoclonal antibody CC49, which was radiolabeled with iodine 125 (125I). A hand-held gamma-detecting probe was used at surgery to detect the radiolabeled antibody. Patients were classified as to the presence or absence of 125I-CC49-positive residual tissue at the close of surgery. Patient survival was analyzed. RESULTS: Follow-up ranged from 30 to 54 months. Survival of 11 stage I or II patients was longer than in 20 stage III or IV patients (P = 0.019). All 14 patients cleared of RIGS-positive tissue were alive at last follow-up, while 15 of 17 RIGS-positive patients died of their disease (P < 0.0001). CONCLUSIONS: The RIGS system used during surgery provides the surgeon with immediate prognostic information on patients with colorectal cancer and supplements traditional pathologic staging.

Triploid abortus presenting as an ectopic pregnancy.

In this article we present a case of an ectopic gestation having morphologic features of a partial hydatidiform mole and demonstrating triploidy by flow cytometry in a patient presenting at 9 weeks' gestation. We include brief comments on partial hydatidiform mole.