PubMed Health⌕ Search

Biomedical subjects

J M Esteban

Publications and source records attributed to J M Esteban.

At least 19 recordsLinked to original sources
PubMed2004

Perfusion CT and angio CT in the assessment of acute stroke.

In order to evaluate the clinical utility of non-enhanced CT with perfusion and angio CT in the assessment of acute ischaemic stroke, 42 patients with symptoms of acute stroke were examined within the first 6 h from onset of symptoms with non-enhanced CT (NECT), perfusion CT (PCT) and CT angiography (CTA). Maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were analysed visually, and after drawing regions of interest (ROIs) in the territory of anterior, middle and posterior cerebral arteries, maximum-intensity projection and volume-rendering images of the cervical and cerebral vessels were created. All patients underwent a control CT or MR examination 24-48 h after the initial examination. Twenty-nine patients developed an area of infarction at control examinations. Significant perfusion abnormalities were found in 27 cases, whilst in two patients the perfusion studies were considered to be normal. All the cases with perfusion abnormalities showed arterial stenoses or occlusions on angio CT. Small infarctions at levels other than the ones selected for perfusion CT, and arteriosclerotic changes, were observed in the two cases with no perfusion abnormalities. In conclusion, combining non-enhanced CT with PCT and CTA is a simple and a very valuable tool in the initial assessment of acute stroke.

Aged↗
PubMed2002

[Value of power Doppler ultrasonography with intravenous contrast medium (Levograf) in the diagnosis of acute cholecystitis].

The aim of this study was to evaluate the potential capacity of color and power Doppler sonography with intravenous contrast medium in the diagnosis of acute cholecystitis. We examined 18 patients with acute cholecystitis, 5 patients with chronic cholecystitis and a control group of 11 patients without gallbladder disease. In these patients, vascularization of the gallbladder wall was evaluated by color and power Doppler sonography before and after intravenous administration of contrast medium (Levograf). Vascularization was evaluated with a 3-point scale (grades 0, 1 and 3) according to the intensity and localization of signs of color. In the diagnosis of acute cholecystitis, basal examination with power Doppler had a sensitivity of 38.8%. After administration of intravenous contrast medium, sensitivity was 100%. In conclusion, the use of sonographic contrast media in the diagnosis of acute cholecystitis showed a sensitivity and specificity of 100%. This technique represents a viable diagnostic alternative to other complementary or imaging studies.

Acute Disease↗
PubMed2002

Improved detection of liver metastases with contrast-enhanced wideband harmonic imaging: comparison with CT findings.

OBJECTIVE: To evaluate the capability of contrast-enhanced wideband harmonic imaging (WHI) to detect liver metastases in comparison with fundamental B-mode US and postcontrast CT. METHODS: We studied 27 patients with hepatic metastases from different malignancies with conventional B-mode sonography, WHI 3 min after injection of contrast agent (Levovist(R) 2.5 g, 300 mg/ml) and postcontrast helical CT (HCT). The number and location of the lesions and the smallest lesion for each patient were noted by two different observers and compared. RESULTS: Both readers recorded an increase in the number of lesions in harmonic mode compared with conventional B-mode in all 27 patients with hepatic metastases with a mean increase in both observers from 9.3 lesions with B-mode to 18.8 lesions with WHI. The smallest lesions were detected with WHI when compared with conventional US and HCT (2 mm with WHI, 5 mm with B-mode and 5 mm with CT). WHI detected more lesions than conventional US or HCT. CONCLUSIONS: Contrast-enhanced WHI seems superior to conventional US and HCT for the detection of hepatic metastases, specially for those nodules under 1 cm of diameter.

Adult↗
PubMed2001

Activity of Crohn's disease assessed by colour Doppler ultrasound analysis of the affected loops.

The aim of this study was to evaluate with colour Doppler ultrasound the vascular changes in the wall of the loops affected by Crohn's disease, and to establish whether these changes reflects clinical or biochemical activity of Crohn's disease. Seventy-nine patients with Crohn's disease (44 with active disease and 35 inactive patients) were studied with frequency- and amplitude-encoded duplex Doppler sonography. A group of 35 healthy volunteers were also included. The exam consisted of the search for colour signals in the walls of the loops affected by Crohn's disease, classifying the degree of vascularity with a simple scoring system into three groups: absence of colour signal (score of 0); weak or scattered colour signals (score of 1); and multiple colour signals or clear identification of vessels in the loops walls (score of 2). Doppler curves were obtained of the detected vessels with measurement of the resistive index (RI). There was a visible increase in the gut walls' vascularity in the active patients compared with those with inactive disease. The mean RI was statistically significantly lower in the gut wall vessels of the patients with active illness than that obtained in the inactive patients. Colour Doppler ultrasound is a useful tool in the assessment of activity in Crohn's disease.

Adolescent↗
PubMed2001

Hepatitis B virus-specific T-cell proliferation and cytokine secretion in chronic hepatitis B e antibody-positive patients treated with ribavirin and interferon alpha.

Immune elimination of hepatitis B virus (HBV) during antiviral therapy depends on the activation of T-cell responses, which are generally impaired in chronic hepatitis B. HBV-specific T helper (Th)-cell reactivity has been assessed post-treatment in liver and peripheral blood of 18 anti-HBe-positive patients with chronic hepatitis B administered combined ribavirin/interferon alfa (IFN-alpha) therapy. The results showed that patients with undetectable HBV DNA by quantitative polymerase chain reaction under combination therapy were able to mount an HBV-specific CD4(+) Th-cell proliferative response and such T-cell reactivity is detectable 1 year after HBV DNA clearance. Hepatitis B virus core (HBcAg) and e (HBeAg) antigen-specific Th-cell proliferation was found more frequently in the liver and peripheral blood in those patients who sustained the alanine aminotransferase (ALT) normalization together with HBV DNA loss. However, HBV-specific IFN-gamma production in vitro in peripheral blood mononuclear cells augmented in 4 of 5 sustained responders and all 13 nonresponders, interleukin 10 (IL-10) production decreased in all 5 sustained responders but increased in 7 of 13 nonresponders. Furthermore, intrahepatic HBcAg plus HBeAg-specific Th-cell proliferation only occurred in sustained responders (2 of 3, 67%, vs. 0 of 9; P =.045) whose cells showed in vitro significantly increased productions in HBcAg/HBeAg-specific IFN-gamma and IL-12 compared with nonresponders in whom IFN-gamma and IL-12 productions decreased together with increased IL-10 secretion. In conclusion this study indicates that combined therapy with ribavirin and IFN-alpha for chronic hepatitis B not only significantly reduces viremia levels but also induces lasting CD4(+) T-cell proliferation and Th1 cytokine release at the site of infection, which may lead to sustained eradication of the HBV.

Adult↗
PubMed1999

Benign metastasizing leiomyoma of the uterus: histologic and immunohistochemical characterization of primary and metastatic lesions.

Benign uterine leiomyoma metastasizing to the lung is a recognized entity that has been reported infrequently in the medical literature. There is persisting controversy regarding the pathogenesis and biology of these lesions. We report a well-studied and well-characterized case of benign leiomyoma metastasizing to the lung. The patient was a 72-year-old woman with an enlarged uterus that contained several leiomyomas with usual histology. Areas of fibrosis, hyalinization, edema, and focal infarction together with small foci with mildly increased cellularity and minimal nuclear pleomorphism were seen. Careful and repeated mitotic counts ranged from 0 to 2 mitoses per 10 high-power fields. In summary, based on histopathologic criteria, the neoplasm was determined to be a focally cellular benign leiomyoma. Four years later, the patient underwent surgical resection of a single nodule in the lung, which had been detected on routine radiographs. Histopathologic evaluation showed a low-grade leiomyosarcoma with moderate nuclear pleomorphism, necrosis, and brisk mitotic activity. Immunohistochemical studies performed on both neoplasms showed them to be of mesenchymal derivation with smooth muscle differentiation. Both neoplasms expressed estrogen receptors with moderate to strong intensity. The patient received no further treatment and, to date, shows no evidence of recurrent disease. The diagnosis of benign metastasizing leiomyoma can only be made with certainty after careful and extensive sampling of the primary tumor to exclude small foci of sarcoma and of the pulmonary tumor to rule out a primary neoplasm. Although it is biologically peculiar, benign metastasizing leiomyoma should continue to be recognized as a distinct entity because current morphologic criteria do not allow primary myometrial tumors to be reclassified as leiomyomas of uncertain malignant potential even if they have metastasized to the lung.

Actins↗
PubMed1998

Dose escalation trial of indium-111-labeled anti-carcinoembryonic antigen chimeric monoclonal antibody (chimeric T84.66) in presurgical colorectal cancer patients.

UNLABELLED: Chimeric T84.66 (cT84.66) is a high-affinity (1.16x10(11) M(-1)) IgG1 monoclonal antibody against carcinoembryonic antigen (CEA). The purpose of this pilot trial was to evaluate the tumor-targeting properties, biodistribution, pharmacokinetics and immunogenicity of 111In-labeled cT84.66 as a function of administered antibody protein dose. METHODS: Patients with CEA-producing colorectal cancers with localized disease or limited metastatic disease who were scheduled to undergo definitive surgical resection were each administered a single intravenous dose of 5 mg of isothiocyanatobenzyl diethylenetriaminepentaacetic acid-cT84.66, labeled with 5 mCi of 111In. Before receiving the radiolabeled antibody, patients received unlabeled diethylenetriaminepentaacetic acid-cT84.66. The amount of unlabeled antibody was 0, 20 or 100 mg, with five patients at each level. Serial blood samples, 24-hr urine collections and nuclear images were collected until 7 days postinfusion. Human antichimeric antibody response was assessed up to 6 mo postinfusion. RESULTS: Imaging of at least one known tumor site was performed in all 15 patients. Fifty-two lesions were analyzed, with an imaging sensitivity rate of 50.0% and a positive predictive value of 76.9%. The antibody detected tumors that were not detected by conventional means in three patients, resulting in a modification of surgical management. Interpatient variations in serum clearance rates were observed and were secondary to differences in clearance and metabolic rates of antibody and antibody:antigen complexes by the liver. Antibody uptake in primary tumors, metastatic sites and regional metastatic lymph nodes ranged from 0.4% to 134% injected dose/kg, resulting in estimated 90Y-cT84.66 radiation doses ranging from 0.3 to 193 cGy/mCi. Thirteen patients were evaluated 1-6 mo after infusion for human antichimeric antibody, and none developed a response. No major differences in tumor imaging, tumor uptake, pharmacokinetics or organ biodistribution were observed with increasing protein doses, although a trend toward increasing blood uptake and decreasing liver uptake was observed with increasing protein dose. CONCLUSION: Chimeric T84.66 demonstrated tumor targeting comparable to other radiolabeled intact anti-CEA monoclonal antibodies. Its immunogenicity after single administration was lower than murine monoclonal antibodies. These properties make 111In-cT84.66, or a lower molecular weight derivative, attractive for further evaluation as an imaging agent. Yttrium-90 dosimetry estimates predict potentially cytotoxic radiation doses to select tumor sites, which makes 90Y-cT84.66 also appropriate for further evaluation in Phase I radioimmunotherapy trials. Although clinically important changes in biodistribution, pharmacokinetics and tumor targeting with increasing protein doses of 111In-cT84.66 were not demonstrated, the results do suggest that antibody clearance from the blood is driven by hepatic uptake and metabolism, with more rapid blood clearance seen in patients with liver metastases. These patients with rapid clearance and potentially unfavorable biodistribution for imaging and therapy may, therefore, be a more appropriate subset in which to evaluate the role of administering higher protein doses. This underscores the need to further identify, characterize and understand those factors that influence the biodistribution and clearance of radiolabeled anti-CEA antibodies, to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.

Adult↗
PubMed1997

Clinical evaluation of indium-111-labeled chimeric anti-CEA monoclonal antibody.

UNLABELLED: Chimeric T84.66 (cT84.66) is a high-affinity (1.16 x 10[11] M[-1]) IgG1 monoclonal antibody (MAb) against carcinoembryonic antigen (CEA). This pilot trial evaluated the tumor-targeting properties, biodistribution, pharmacokinetics and immunogenicity of 111In-labeled cT84.66. METHODS: Patients with CEA-producing metastatic malignancies were administered a single intravenous dose of 5 mCi 111In-diethylenetriaminepentaacetic acid-cT84.66. Serial blood samples, 24-hr urine collections and nuclear images were collected up to 7 days postinfusion. Human antichimeric antibody response was assessed up to 6 mo postinfusion. RESULTS: Imaging of at least one known tumor site was observed in 14 of 15 (93%) patients. Seventy-four lesions were analyzed with an imaging sensitivity rate of 45.1% and a positive predictive value of 94.1%. In one patient, two additional bone metastases developed within 6 mo of antibody administration at sites initially felt to be falsely positive on scan. One patient developed a human antichimeric antibody response predominantly to the murine portion of the antibody. The antibody cleared serum with a median T(1/2alpha) of 6.53 hr and a T(1/2beta) of 90.87 hr. Interpatient variations in serum clearance rates were observed and were secondary to differences in clearance and metabolic rates of antibody-antigen complexes by the liver. One patient demonstrated very rapid clearance of antibody by the liver, which compromised antibody localization to the primary tumor. Antibody uptake in primary and metastatic tumors ranged from 0.5% to 10.5% injected dose/kg, resulting in estimated radiation doses ranging from 0.97 to 21.3 cGy/mCi 90Y. Antibody uptake in regional lymph nodes ranged from 1.3% to 377% injected dose/kg, resulting in estimated radiation doses ranging from 2.0 to 617 cGy/mCi 90Y. CONCLUSION: Chimeric T84.66 demonstrated tumor targeting that was comparable to that of other radiolabeled intact anti-CEA Mabs. Its immunogenicity after single administration was lower than murine Mabs. These properties make cT84.66 or a lower molecular weight derivative attractive for further evaluation as an imaging agent. These same properties also make it appropriate for future evaluation in Phase I therapy trials. Finally, a wide variation in the rate of antibody clearance was observed, with one patient demonstrating very slow clearance, resulting in the highest estimated marrow dose of the group, and one patient demonstrating unusually rapid clearance, resulting in poor antibody localization to tumor. Data from this study suggest that serum CEA levels, antibody-antigen complex clearance and, therefore, antibody clearance are influenced by both the production and clearance rates of CEA. This underscores the need to further identify, characterize and understand those factors that influence the biodistribution and clearance of radiolabeled anti-CEA antibodies to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.

Adult↗
PubMed1996

Endothelial area as a prognostic indicator for invasive breast carcinoma.

BACKGROUND: Vascular enumeration using antibodies to Factor VIII has been reported to be an independent prognostic indicator of invasive breast carcinoma. METHODS: To eliminate potential subjectivity in distinguishing between individual vessels, especially in areas of tangled capillaries, total endothelial area (EA) was assessed using a Samba 4000 image analyzer. One hundred seventy-eight invasive breast carcinomas (Stage 1 and 2, mean follow-up: 71 months) were immumostained for the presence of CD34, the human hematopoietic progenitor cell antigen also present in endothelium, and EA was quantitated within 5 adjacent 20X fields (0.74 mm2). Additionally, these same vessels were manually counted from the image analyzer. Manual counts were also made from a photomicrograph representative of a single 10X field (1.06 mm2). RESULTS: High grade carcinomas contained greater endothelial area than low grade carcinomas (P = 0.0001). Endothelial area was prognostically significant (P = 0.004) in univariate analysis of disease-free survival (DFS) and overall survival (OS), as were stage of disease, tumor size, and combined histologic grade (P < or = 0.024). Manual vessel counts from the monitor were significant for OS only. Manual vessel counts from photomicrographs showed no statistically significant association with DFS or OS. In multivariate analysis, EA, but not vessel enumeration, remained as an independent predictor for OS (lymph node negative patients only, n = 87) and for DFS (lymph node positive patients only, n = 91). For the entire group of patients (lymph node negative and lymph node positive) independent predictors of DFS and OS were tumor grade and size (P < or = 0.006). CONCLUSIONS: Of the three methods used to evaluate tumor angiogenesis, total endothelial area, as objectively evaluated by image analysis, was the only independent prognostic indicator for OS for patients with lymph node negative invasive breast carcinoma.

Adult↗
PubMed1996

Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2.

Earlier evidence suggests that transforming growth factor beta (TGF beta) plays a significant role in tumor progression and metastasis. The most likely mechanism of the action of TGF beta is induction of immunosuppression in the host, allowing for unchecked tumor growth and metastasis. We attempted to test that hypothesis and to compare antitumor effects of anti-TGF beta antibody alone and in combination with interleukin-2 (IL-2). Six- to 8-week-old female C57B1-6 mice were induced with murine B16 melanoma by tail vein injection. Therapy was started 48 h after tumor injections. Monoclonal anti-TGF beta antibody (2G7) was administered intraperitoneally (i.p.) at 500 micrograms every other day, and IL-2 at 10,000 U i.p. twice daily, for 21 days. A threefold decrease in the number of lesions in the anti-TGF beta/IL-2 treatment group compared with the control group was observed, a highly significant statistical difference (p = 0.002). No statistically significant differences were seen between the control group and other studied groups (IL-2 alone, anti-TGF beta alone). Analysis of TGF beta levels in plasma by the TGF beta-1 Quantikine assay indicated normal levels in the control and IL-2 groups, and significantly diminished levels in the two groups that received TGF beta antibody. However, acid-ethanol extraction of plasma (to reverse antibody binding before assay) showed normal plasma TGF beta levels in all groups, suggesting that the antibody may alter the availability of TGF beta in vivo. Microscopic analysis of metastases revealed a decrease in the average size of lesions in the groups treated with IL-2. Thus, combination therapy using anti-TGF beta antibody and IL-2 may be a novel, less toxic approach to tumor immunotherapy.

Animals↗
PubMed1995

Initial experience evaluating 90yttrium-radiolabeled anti-carcinoembryonic antigen chimeric T84.66 in a phase I radioimmunotherapy trial.

Chimeric T84.66 (cT84.66) is a high-affinity (5 x 10(10) M-1) anti-carcino-embryonic antigen (CEA) IgG1. In a recently completed pretherapy imaging trial, 111In-labeled cT84.66 demonstrated targeting of CEA-producing metastatic sites and low immunogenicity, with human antichimeric antibody (HACA) response in only 1 of 15 patients after a single administration. The purpose of the present study was to evaluate cT84.66-diethylenetriaminepentaacetic acid labeled with 90Y in a dose-escalation Phase I trial. Patients with metastatic CEA-producing malignancies received imaging doses of 5 mCi 111In-labeled cT84.66 first, followed 1-2 weeks later by 5 mg cT84.66 labeled with the therapeutic dose of 90Y. Immediately following the therapeutic infusion, diethylenetriaminepentaacetic acid was administered by continuous i.v. infusion over 3 days at 250 mg/m2 body surface area/24 h. Biodistribution, tumor targeting, absorbed radiation dose estimates, antibody clearance, and HACA response were evaluated through blood samples, 24-h urine collections, and nuclear images performed at serial time points after infusion. To date, three patients with metastatic colorectal cancer have been evaluated at the first dose level of 5 mCi/m2. No side effects were associated with antibody administration. Localization of the antibody to nonhepatic metastatic sites was observed. Size-exclusion high-performance liquid chromatography demonstrated the formation of CEA:antibody complexes in serum in all three patients. A significant variation among patients in the clearance rate of the antibody and complexes from blood to liver was seen, which resulted in a reciprocal relationship between estimated liver dose and red marrow dose. Patients who demonstrated faster clearance to liver demonstrated greater excretion of a low-molecular-weight metabolite through the urine. Two patients developed HACA response, which persisted at 4 months after therapy. At this first dose level, no tumor responses were seen and reversible grade 1 thrombocytopenia was observed in 2 patients. cT84.66 demonstrated effective localization in CEA-producing tumors. Its low immunogenicity after a single administration makes it attractive for further evaluation as a radioimmunotherapeutic agent. However, further evaluation is needed to determine whether its immunogenicity will remain low after multiple administrations. Additionally, in two of the three patients, we identified rapid clearance of the antibody to the liver. This underscores the need to identify, characterize, and understand further those factors that influence the biodistribution and clearance of anti-CEA antibodies to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.

Carcinoembryonic Antigen↗
PubMed1995

gamma-Interferon administration after 90yttrium radiolabeled antibody therapy: survival and hematopoietic toxicity studies.

PURPOSE: Hematopoietic toxicity is the dose-limiting factor for radioimmunotherapeutic regimens. Cytokines have been shown to decrease hematopoietic toxicity in animals exposed to whole-body irradiation. The purpose of this study was to investigate the effects of murine gamma-interferon (gamma-IFN) on survival and hematopoietic toxicity in mice treated with high dose 90yttrium labeled anticarcinoembryonic antigen (CEA) monoclonal antibody. METHODS AND MATERIALS: Balb/c nu/nu mice were injected intravenously with 250 Ci 90Y-T84.66 (a murine anti-CEA monoclonal antibody). Thirty thousand units of gamma-IFN was administered i.v. 24 h later. Control mice received either 250 Ci 90Y-T84.66 alone or 30,000 units gamma-IFN alone. Survival, antibody biodistribution, and bone marrow histologic studies were then performed. RESULTS: Only 7% of the animals treated with 90Y-T84.66 survived up to 40 days posttreatment, when the study was terminated. In contrast, 52% of the mice treated with both 90Y-T84.66 and gamma-IFN survived 40 days posttherapy. No toxic deaths were seen in the control group administered gamma-interferon alone. Histologic examination of the bone marrow of animals receiving 90Y-T84.66 and gamma-IFN showed cellular depletion of 40-70% of the hematopoietic cells by 48 h. Cell depletion was 50-70% and 20% by 72 h and 8 days posttherapy, respectively. The marrow of the 90Y-T84.66-treated control group was depleted to a level of 50-80% at 48 h, and remained depleted at 90% at 72 h and 8 days posttherapy. No marrow cell reduction was seen in the gamma-IFN-only treated group. Biodistribution studies showed no alterations in antibody biodistribution or kinetics that could account for the changes in bone marrow toxicity after gamma-IFN. CONCLUSION: These results demonstrate that gamma-IFN can reduce the hematologic toxicity resulting from high dose radioimmunotherapy. Histologic studies of bone marrow suggest that gamma-IFN acts primarily to accelerate myelorestoration of the bone marrow. Further studies exploring the use of gamma-IFN as an adjunct to radioimmunotherapy are therefore warranted.

Animals↗
PubMed1995

Skin biopsy in allogeneic and autologous bone marrow transplant patients: a histologic and immunohistochemical study and review of the literature.

Histologic criteria and grading system for diagnosis of cutaneous manifestations of graft vs. host disease (GvHD) have been established, and the diagnosis of high-grade GvHD is readily made by pathologists. There have been, however, increasing reports of skin rash occurring in patients treated with autologous bone marrow transplant (aBMT) that cannot be distinguished clinically or histologically from GvHD following allogeneic bone marrow transplant (alloBMT). We studied the histologic and immunohistochemical features of 25 skin biopsy specimens obtained from 22 patients with skin rashes who had undergone either aBMT or alloBMT, or who suffered from a malignancy. Tissue sections were immunoreacted with pan-T lymphocyte-associated antibody Leu 22 (CD43); pan-B antibody L26 (CD20); macrophage/myeloid antibody for CD68 antigens; and LN-3 antibody specific for HLA Class II antigens. The clinical suspicion of GvHD was confirmed in 8 of 10 alloBMT patients. Seven of the 10 aBMT patients also clinically diagnosed to have GvHD, had histologic changes consistent with Grades I, II, or III. The rest of the patients showed changes consistent with drug reaction. T-cell lymphocytes (Leu22), macrophages (CD68), and HLA-DR expression on Langerhans cells were in general more prominent in allogeneic chronic GvHD, but this was not statistically significant. No significant differences were seen in the degree of HLA-DR expression on endothelial cells and keratinocytes in any of the groups. The current histologic criteria are inadequate to differentiate cutaneous GvHD following alloBMT from the skin rash occurring in the setting of aBMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1994

Prognostic relevance of carcinoembryonic antigen and estrogen receptor status in breast cancer patients.

BACKGROUND: Expression of carcinoembryonic antigen (CEA) has been reported in 10-95% of breast cancer. Its value as a predictor of disease progression is controversial. METHODS: The expression of CEA in 202 Stages I and II breast carcinomas was assessed by immunohistochemistry, and the results were correlated with various histologic and clinical parameters to establish CEA's biologic relevance. The mean follow-up of the patients was 6.5 years. The monoclonal antibody used does not cross-react with other molecules in the CEA gene family. RESULTS: One hundred, thirteen (56%) tumors expressed CEA in more than 15% of the cells. Expression of CEA was associated with positive estrogen receptor (ER) status (P = 0.003). Univariate Cox regression analysis showed that, whereas disease free survival (DFS) and overall survival (OS) were not associated significantly with CEA expression, tumor size, nuclear grade, ER status, lymph node metastases, and stage were. When ER status was stratified to CEA expression, patients who were ER negative and had CEA-negative tumors had a 3.9 times higher risk (P = 0.032) of death than did the patients with CEA-positive tumors. Cox regression analysis revealed that ER was the only parameter with significant interacting effect with CEA. Multivariate, stepwise Cox regression analysis showed that CEA expression, tumor size, and nuclear grade were the only significant independent predictors of DFS, and nuclear grade and lymph node metastasis the only significant predictors of OS in the ER-positive group. The only significant independent predictor of DFS and OS in the ER-negative group was CEA. When CEA expression was stratified to ER status, patients whose tumors lacked CEA and ER had threefold higher risk of disease relapse (P = 0.002) and a 5.3-fold higher risk of death (P = 0.0001) than those with ER-positive and CEA-negative tumors. Multivariate analysis showed that the association between CEA and ER was enhanced further after compensating for other parameters with independent predictive value. CONCLUSIONS: The association between CEA and ER was the most important independent predictor of a subgroup of patients (CEA-negative, ER-positive) with the most favorable prognosis. The results imply that the association of several tumor markers may provide tumor profiles with superior predictive value than a single parameter.

Antibodies, Monoclonal↗
PubMed1994

Biologic significance of quantitative estrogen receptor immunohistochemical assay by image analysis in breast cancer.

The authors assayed 209 stage I and II mammary carcinomas for the estrogen receptor (ER) with an immunocytochemical assay (ICA) and quantitated the nuclear stain with the SAMBA 4000 Cell Image Analysis System (Imaging Products International, Inc., Chantilly, VA). The cases had been followed for 54-214 months (average, 64 months). The results were correlated with the patients' overall and disease-free survival times. Three of the parameters obtained from the quantitative analysis were evaluated: labeling index, mean optical density, and quick score. Statistical analysis was performed with the Kaplan-Meier product limit estimator for quantitated values and Cox regression for risk of mortality and disease progression. Mean optical density of the nuclei at a cut-off value of 10 produced the strongest association between quantitative ERICA and overall and disease-free survival times in discriminating high- and low-risk groups (P = .016 and P = .018, respectively). When the mean optical density results were categorized into ranges of values of potential biologic significance according to overall survival times, patients with mean optical density greater than 15 were found to be at lowest risk; patients with values between 5 and 15 had a statistically significant intermediate risk; and the group with values less than 5 had the worst outcome (P = .018). The probability of disease-free survival also was statistically significant (P = .038) among the three groups with cut-off points of less than 10, 10-35, and greater than 35. These results showed that quantified optical density has better discriminating power for risk prediction than that obtained by the biochemical assay for ER at a cut-off value of 10 or 20 fmol/mg. Estrogen receptor ICA has been adequately shown to be as or more accurate than ligand-binding assays. Our results corroborate those studies and support the utility of ICA assays for ER by showing that quantitation performed by image analysis is an objective and reproducible method yielding clinical prognostic information of higher reliability than that given by the dextran-coated charcoal ER assay.

Adult↗
PubMed1994

Quantitative immunohistochemical assay for hormonal receptors: technical aspects and biological significance.

Over 250 breast carcinomas were studied in order to establish whether or not quantitative immunohistochemical assays (ICA) for estrogen and progesterone receptors (ER and PR) with computer-assisted image analysis could favorably compare with standard cytosolic assays. Initially, variable antigenic preservation secondary to improper tissue fixation and processing led to irregular receptor preservation and unevenly stained areas indistinguishable from true intratumor antigenic heterogeneity. As a direct consequence of the field selections chosen for analysis, assay reproducibility was less than optimal. Proper tissue fixation and handling eliminated most of the irregular staining; selection of fields to analyze became less cumbersome and more reproducible. Differences in staining intensity due to minimal variations in the ICA also resulted in difficult reproducibility. Standardizing the technique and using an automatic stainer notably eliminated that problem. The second and equally important question was to establish if quantitative ER-ICA had relevance as a predictor for prognosis. The Kaplan-Meier product limit estimator for quantitated ER values and Cox regression for risk of mortality and disease progression were performed. The results obtained discriminated high- and low-risk groups for overall survival (p = 0.016) better than the dextran-coated charcoal assay. Elimination of two major obstacles and proof of the predictive value of quantitative ICA has transformed the assay into a valid alternative to cytosolic methods; however, before that takes place it is critical to establish standard procedures for both ICA and quantitation so interlaboratory variability is reduced to a minimum.

Adult↗