Search PubMed⌕ Search

Biomedical subjects

H Battifora

Publications and source records attributed to H Battifora.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Immunohistochemical detection of bcl-2 and MIB-1/Ki-67 in breast cancer: retrospective analysis of 238 cases].

We considered of interest to determine the possible interrelationship between the proliferation-related marker MIB-1/Ki-67 and the bcl-2, a protein involved in the blockage of apoptosis, and whether they contributed to the prognosis of breast cancer. For this purpose we carried out a retrospective immunohistochemical study of 238 cases of stage I and II breast carcinomas with a follow up of at least 5 years. The study revealed that high expression of MIB-1 was associated with high nuclear and histological grades (p < 0.001 for both), negative estrogen receptor status (p = 0.009) and progesterone status (p = 0.004), and younger age (p = 0.014). High bcl-2 expression was associated with smaller tumor size (p = 0.001), positive estrogen and progesterone receptors (p < 0.001 for both); low nuclear grade (p < 0.001), low histological grade (p < 0.002), stage I disease (p = 0.01) and low MIB-1 expression (p = 0.025). The univariate Cox regression showed a significant association of high MIB-1 expression (p = 0.002) and low bcl-2 expression (p = 0.04) with shorter OS. Furthermore, MIB-1 expression was a significant independent predictor of OS (p = 0.002) as showed by stepwise Cox regression analysis.

Antibodies, Monoclonal↗
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↗
PubMed1994

[Expression of p53 in gastric carcinoma. Prognostic value].

P53 gene mutation has been described with variable frequency in gastric cancer and its biological significance remains unclear. We studied 101 gastric carcinomas to evaluate the association between this genetic alteration and the evolution of gastric cancer. Of these, 67 patients were men and 34 were women. The median age at diagnosis was 68 years. The tumors were obtained from gastrectomies. The p53 gene mutation was determined with the monoclonal antibody DO7 (Novocastra). The neoplasms were classified as tumors with high or low level p53 expression according to the intensity and distribution of the nuclear staining. Forty eight tumors showed high level of p53 immunoreactivity. The association of p53 expression with age, sex, tumor size, histologic type, histologic grade, depth of invasion, localization, lymph node metastases, type of surgery and 5 year survival rate was investigated. The results did not demonstrate any significant association between p53 expression and the factors mentioned above.

Adenocarcinoma↗
PubMed1994

Predictive value of estrogen receptors evaluated by quantitative immunohistochemical analysis in breast cancer.

To establish the reliability and biologic importance of quantitative immunohistochemical assays for estrogen receptors, more than 200 stage I and II breast cancers were studied. Immunohistochemical analysis was performed using antibody ER 1D5 (AMAC Westbrook, ME) in an automatic stainer (Tech Mate, Biotek, Santa Barbara, CA). Nuclear stain was quantitated by image analysis (SAMBA 4000; IPI, Chantilly, VA). Statistical analyses were performed using Kaplan-Meier product limit estimator for quantitated values and Cox regression for risk for death and disease progression. Estrogen receptor values obtained using the dextran-coated charcoal method were available for comparison. Quantitated immunohistochemical values, expressed as mean optical density of stained nuclei, could discriminate groups of patients that had as much as 3 times higher risk for death and 2.5 times higher risk for disease relapse (P = .006 and P = .018, respectively). Patients could be divided into three risk groups, based on their overall and disease-free survival, that were statistically significant (P = .018). The same analysis was performed using biochemically assayed estrogen receptors values showing that at a cutoff value of 20 fmol/mg, estrogen status predicted overall survival, albeit with lesser probability values (P = .032). These results show that quantitative immunohistochemistry of estrogen receptors provides results that have better predictive value than the biochemically procured ones. This approach not only obviates many pitfalls of the methods requiring tissue homogenates but also allows simultaneous correlation with histopathologic tumor features and expression of other relevant markers.

Breast Neoplasms↗
PubMed1993

Prognostic significance of immunohistochemical analysis of cathepsin D in low-stage breast cancer.

BACKGROUND: Cathepsin D is an estrogen-regulated lysosomal protease that may be overexpressed in breast cancer. Several studies based on biochemical analysis of tumor cytosol have shown that high levels of cathepsin D are associated with poor outcome in patients with breast cancer. In contrast, a few immunohistochemical studies have shown that cathepsin D positivity in breast cancer cells indicates a favorable prognostic outcome or is of no prognostic significance. METHODS: Because of the current controversy, the authors studied, using immunohistochemistry, the distribution (0 to 3) and intensity (0 to 3) of cathepsin D in Stage I and II infiltrating ductal carcinoma of the breast from 245 patients treated at the City of Hope National Medical Center, Duarte, California, from 1970 to 1986. A commercially available rabbit antiserum to purified human cathepsin D and the standard avidin-biotin complex method were used. Statistical analysis was based on a combined low (0 or 2) or high (3 to 6) score. RESULTS: A high cathepsin D score was associated with Stage II disease (P = 0.007), positive lymph nodes (P = 0.019), high nuclear grade (P = 0.005), and c-erbB-2 oncogene amplification (P = 0.013). Cathepsin D positivity was not an independent prognostic indicator of disease-free survival (DFS) or overall survival (OS). In a subgroup analysis, the presence of cathepsin D had only a modest association with predicting a shorter DFS in patients with negative lymph nodes (P = 0.072) or positive progesterone receptors (PR) (P = 0.086). CONCLUSIONS: Immunohistochemical analysis of cathepsin D, with the antiserum used in this study, is not an independent predictor of outcome in patients with breast cancer because of its strong associations with several well-established prognostic indicators.

Adult↗
PubMed1993

Sensitivity and specificity of Gold types 1 to 5 anti-carcinoembryonic antigen monoclonal antibodies: immunohistologic characterization in colorectal cancer and normal tissues.

Carcinoembryonic antigen (CEA) is one of the better-studied oncodevelopmental antigens to which numerous monoclonal antibodies (MoAbs) have been generated. Many of these MoAbs have been recently grouped (Gold classification) according to their epitope recognition. The present study was designed to immunocharacterize various MoAbs, each representative of the five Gold groups, on colorectal cancers and normal tissues using semiquantitative immunohistochemistry. Sensitivity, based on the number of colorectal cancer cases (n = 100) with positive reaction (> 5% cells), was greater with Gold groups 1 and 2 (93% each) than with groups 3, 4, and 5 (78%, 83%, and 87%, respectively). The intensity of the strain also correlated with the Gold groups, with 24%, 20%, and 18% of cancer cases displaying weak or negative staining (0 or 1+) when reacted with MoAbs from groups 3, 4, and 5, respectively, versus 6% and 12% with Gold 1 and 2 antibodies. Cross-reactivity of the anti-CEA antibodies with CEA-related molecules was found to be significant with Gold 5 antibody, which stained most of the normal lung, liver, stomach, and intestinal tissues tested. Strong staining also was seen in granulocytes when they were reacted with Gold 4 and 5 antibodies. The other antibodies showed much less and variable cross-reactivity with normal tissues, with a not statistically significant advantage for Gold 1 antibodies. In addition to lower sensitivity in CEA detection, Gold 3 to 5 MoAbs were less specific due to cross-reaction with one or more of the CEA-related macromolecules expressed by normal tissues. Based on these results and given the broad clinical applications of anti-CEA MoAbs, it is essential to characterize each MoAb to be used for clinical purposes in order to avoid interpretation errors of potential relevance resulting from poor sensitivity/specificity. The use of antibodies that recognize the epitope of group 1 or 2 is recommended to maximize sensitivity and specificity for CEA detection.

Antibodies, Monoclonal↗
PubMed1993

Improvement of the quantification of estrogen and progesterone receptors in paraffin-embedded tumors by image analysis.

It has been shown previously that estrogen receptors (ER) detected by immunohistochemical examination of paraffin-embedded tissue sections could be quantified by computerized image analysis. Several factors were identified that were, in part, responsible for the modest correlation obtained with biochemical assay results. In the present study, 45 formalin-fixed, paraffin-embedded breast carcinomas from a previous study were reevaluated to determine if current methods could provide a better correlation and more consistent results. Sections of the tumors were made to react with estrogen and progesterone receptor antibodies (ER-ICA and PgR-ICA) and the intensity of the stain was quantified using an image analysis system. Vimentin immunostain was used to assess the degree of antigenic loss. Quantitation was performed only on the areas with nuclear staining. The correlation of the estrogen and progesterone receptor values obtained by the dextran charcoal-coated method with the percentages of stained areas and with the intensity of the stain was excellent. The agreement between both methods was 91.1% for estrogen and 86.7% for progesterone receptor values. These results represent a significant improvement compared with those found in a previous study (87% agreement for estrogen receptor). The current approach to estrogen and progesterone receptor quantitation is simplified and eliminates subjectiveness in the selection of the fields for evaluation. The studies are reproducible because discrepancies due to sampling techniques are excluded. Finally, the method validates the technique as a substitute for cytosol-based methods. The results of the two vastly dissimilar assays, the pitfalls of the "gold standard" dextran charcaol-coated assay, and the need for retrospective studies to acquire a range of quantified ER-ICA and PgR-ICA values with clinical significance are discussed.

Breast Neoplasms↗
PubMed1993

Vimentin-negative epithelioid sarcoma. The value of an immunohistochemical panel that includes CD34.

Virtually all reported cases of epithelioid sarcoma have been vimentin rich, and the coexpression of vimentin and keratin is considered a characteristic immunophenotype in these tumors. We report three cases of soft tissue tumors with histologic and clinical features consistent with epithelioid sarcoma, all of which failed to immunoreact by standard immunohistochemistry for vimentin using two different monoclonal antibodies. Antigen retrieval demonstrated focal vimentin staining in one case, whereas the other two remained negative. An extensive panel of immunohistochemical stains revealed strong diffuse staining with keratin and epithelial membrane antigen in all three cases as well as patchy membrane staining with an antibody to CD34. CD34 positivity is commonly seen in epithelioid sarcoma, but it is very rarely found in carcinomas. We conclude that these cases represent a unique immunophenotypic variant of epithelioid sarcoma that can be immunohistochemically confirmed, despite the lack of identifiable vimentin, by their immunoreactivity for keratin and CD34.

Adult↗
PubMed1993

Keratin gene expression in non-epithelial tissues. Detection with polymerase chain reaction.

Keratin filament are characteristically present in epithelial cells and tumors, but have also been detected in many normal and neoplastic non-epithelial cell types using immunohistochemical techniques. To investigate the validity of this seemingly aberrant protein expression, we applied the highly sensitive polymerase chain reaction (PCR) technique to study keratin gene expression in a variety of non-epithelial tissues. Total RNA was extracted from nine samples of leiomyosarcoma, four non-Hodgkin's lymphoma, seven normal bone marrows, normal lymph node, normal peripheral blood cells, freshly isolated and cultured endothelial cells, cultured skin fibroblasts, and the myeloid leukemia cell line HL-60. Amplification primers and probes for the three most primitive keratin types (8, 18, and 19) were synthesized using published gene sequences. RNA from the breast carcinoma cell line MCF-7, known to be rich in all three keratins, was used as positive control. Concurrently run actin primers were used to confirm RNA integrity. After an initial cycle with reverse transcriptase, PCR amplification was performed for 30 cycles. Southern blots of the PCR products showed variably intense bands corresponding to keratin 8 and 18 gene products in all samples, offering conclusive evidence of keratin gene expression in cells of both stromal and hematopoietic derivation. However, keratin 19 gene transcription was not nearly so ubiquitous, being detected in normal fibroblasts and endothelial cells, two of four non-Hodgkin's lymphoma and four of nine leiomyosarcoma, but not in normal lymph node, peripheral blood cells, HL-60 cells, or any of the seven normal bone marrows examined. Dilutional experiments showed PCR to be highly sensitive in the detection of keratin 19 gene expression, capable of registering one MCF-7 cell in 10(6) HL-60 cells. These studies show that variable levels of keratin 8 and 18 gene expression may be detected by PCR in a wide variety of non-epithelial tissues, supporting previous immunohistochemical and phylogenetic studies. However, keratin 19 gene expression appears to be more restricted and was not evident in any hematopoietic cells devoid of contaminating stromal elements. These findings suggest a role for PCR in the detection of epithelial micrometastasis in certain sites, particularly bone marrow.

Base Sequence↗
PubMed1992

Tumor-associated antigen 43-9F is of prognostic value in squamous cell carcinoma of the lung. A retrospective immunohistochemical study.

BACKGROUND: Squamous cell lung carcinoma (SLC), the most frequent type of lung cancer, generally is treated surgically and its prognosis is poor. The only current clinically useful prognostic criterion is lymph node staging (TNM classification). Expression of a novel tumor-associated carbohydrate epitope Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3 Gal beta 1-4Glc identified by the 43-9F monoclonal antibody (MoAb) is associated with the growth pattern of SLC cell lines in athymic mice and in vitro. This implies that the 43-9F epitope may be related to tumor progression in patients with SLC and that, as such, it could be of prognostic value. METHODS: Primary tumor specimens from 231 patients with lung carcinoma (130 with SLC, 64 with adenocarcinoma, 10 with small cell carcinoma, 16 with large cell carcinoma, and 11 with adenosquamous carcinoma) were examined by immunohistochemical studies on formalin-fixed, paraffin-embedded tissue samples for immunoreactivity with an MoAb to the 43-9F antigen. Univariate and step-wise Cox regression analyses were used to compare survival time by histopathologic diagnosis, smoker status, TNM classification, and type of surgical treatment. RESULTS AND CONCLUSIONS: Patients with 43-9F epitope-positive SLC tumors had a significantly (P less than 0.01) better prognosis than patients with epitope-negative tumors. In contrast, no association was seen between 43-9F epitope expression and survival time for patients with lung adenocarcinomas. Further, the prognostic value of 43-9F expression in SLC was found to be superior to the N-classification with the added advantage that it requires access only to primary tumor tissue and thus is available before therapy.

Adult↗