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H F Frierson

Publications and source records attributed to H F Frierson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Thromboxane receptor blockade improves oxygenation in an experimental model of acute lung injury.

BACKGROUND: Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome. METHODS: Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation. RESULTS: Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences. CONCLUSIONS: Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.

Animals↗
PubMed1996

Quantitative image cytometry of infiltrating ductal carcinoma: comparison with prognostic parameters and reproducibility of histological grade.

Quantitative image cytometry was used to compare 18 parameters relating to ploidy, nuclear area, and chromatin texture to axillary lymph node status, tumor size, and histological grade for 34 infiltrating ductal carcinomas, each of which had been graded independently by each of six surgical pathologists. Zinc formalin-fixed, paraffinembedded tumors were assessed using the Elston and Ellis modification of the Bloom and Richardson histological grading scheme. When axillary lymph node-negative tumors were compared with those involving four or more nodes, % 2 c (diploid) cells, nuclear area, and eight of 12 chromatin texture parameters showed statistically significant differences. Carcinomas < 2 cm had more % 2 c (diploid) cells and fewer % > 4 c (hypertetraploid) cells than larger neoplasms. For tumors having nuclear pleomorphism score two versus those with score three, nuclear area, four of five parameters related to ploidy level, each of five parameters related to run-length matrix features and one of four co-occurrence matrix features showed significant differences. Nearly all of these cytometric parameters also showed significant differences for histological grade and mitotic count, which was strongly correlated with nuclear pleomorphism. In examining the cytometric parameters in relation to the interobserver reproducibility of histological grade and its components, the largest number of statistically significant parameters related to the nonreproducibility of nuclear pleomorphism. The findings indicate that as the grade of infiltrating ductal carcinomas increases, there are fewer % 2 c (diploid) cells and more % > 4 c (hypertetraploid) and % > or = 5 c (polyploid) cells. In addition, the cells of high grade tumors have larger nuclear areas and more small and large dense chromatin clumps, which increase in such number that they tend to join together. When compared with the cytometric parameters, nuclear pleomorphism is the most sensitive component of grade to nonreproducibility.

Breast Neoplasms↗
PubMed1996

Automated immunohistochemical assay for estrogen receptor status in breast cancer using monoclonal antibody CC4-5 on the Ventana ES.

Determination of breast cancer estrogen receptor (ER) status as a predictor of tumor response to adjuvant endocrine therapy remains a mainstay of breast cancer management. Recent second generation anti-ER antibodies and new epitope retrieval methods have produced paraffin-based immunohistochemical results that correlate closely with the dextran-coated charcoal (DCC) assay and appear to represent a superior method of ER assay. The authors determined the ER status of 103 invasive breast cancers by paraffin-based, automated immunohistochemistry on the Ventana ES using a new monoclonal antibody, CC4-5, and compared the results to those of parallel DCC biochemical analysis and manual immunohistochemical analysis using anti-ER monoclonal antibody ER1D5. The specificity of the CC4-5 antibody for ER protein was confirmed by Western blot analysis. Sixty of 103 cases were positive for ER by CC4-5 automated immunohistochemistry. With a ligand binding assay threshold value of 20 fmol/mg protein, there were 50 positive cases by biochemical assay. The biochemical results corresponded to an 88% rate of agreement with automated CC4-5 staining. Analysis of discordant cases revealed that the majority of CC4-5 immunopositive only cases (8 of 11) were strongly positive, stroma rich tumors, suggesting that corresponding biochemical measurements were diluted by non representative stromal tissue. There was only one immunonegative, biochemically positive case (27 fmol/mg protein). Semiquantitation of CC4-5 staining using percent positive tumor cells or weighted average staining intensity (HSCORE) showed moderate to good correlation with quantitative DCC results (r = 0.64 and 0.62, P < .0001). ER1D5 was not suitable for use on the Ventana ES, most likely due to temperature constraints of the instrument. By manual ER1D5 staining, 40 of 79 examined cases were positive corresponding to a 99% rate of agreement with automated CC4-5 staining. Semiquantitation of ER1D5 staining by percent positive tumor cells and weighted average staining intensity (HSCORE) showed excellent correlation with semiquantitation of automated CC4-5 results (r = 0.90 and 0.88, P < .0001). Automated immunohistochemistry using the Ventana ES and monoclonal antibody CC4-5 is a reliable method for determining breast cancer ER status. As with other immunohistochemical methods, direct correlation with morphology precludes errors due to tissue sampling, allowing for accurate analysis of stroma-rich or partially necrotic tumors and small neoplasms that otherwise would yield insufficient tumor tissue for biochemical analysis.

Antibodies, Monoclonal↗
PubMed1996

Human papillomavirus and Epstein-Barr virus in sinonasal Schneiderian papillomas. An in situ hybridization and polymerase chain reaction study.

Using the polymerase chain reaction (PCR), it has been recently reported that the Epstein-Barr virus (EBV) is present in the majority of Schneiderian sinonasal papillomas (SNP) of the inverted type and may play a role in the pathogenesis of these lesions. The reported prevalence rates of human papillomavirus (HPV) in different types of SNP is also controversial and in need of clarification. Twenty-eight SNP from 27 patients were histologically classified and evaluated for evidence of EBV using PCR and 2 different sensitive and specific in situ hybridization (ISH) procedures for EBER1. Similarly, two methods of ISH were also used for the detection of HPV, using biotinylated DNA probes sensitive for 14 different HPV types as well as more sensitive and specific radioactive RNA probes for HPV types 6, 11, and 16. Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for EBER was detected in rare stomal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16. Of the five fungiform SNP, four showed foci of koilocytosis. The results indicate that EBV is not present in sinonasal papillomas. The presence of EBV positive stromal lymphocytes in these lesions may account for a proportion of PCR-positive cases. Oncocytic SNP are unassociated with HPV, whereas inverted SNP contain HPV in a minority of cases. In contrast, fungiform SNP are consistently associated with HPV types 6 and 11 and usually show histologic evidence of viral infection.

Adolescent↗
PubMed1996

Immunohistochemical detection of gamma-glutamyl transpeptidase in normal human tissue.

We developed a new, highly specific antibody that localizes gamma-glutamyl transpeptidase (GGT) in formalin-fixed sections of human tissue. The specificity of the antibody, GGT129, is demonstrated by immunostained Western blots of whole cell homogenate from five different tissues. The utility of the antibody is shown by a comprehensive study of GGT expression in normal human tissue. This study reveals GGT expression for the first time in a number of tissues, including glands in the endocervix, endometrium, and adrenals. Strong immunoreactivity was observed on the surface of renal proximal tubule cells, hepatic bile canaliculi, and capillary endothelial cells within the nervous system. Secretory or absorptive cells in sweat glands, prostate, salivary gland ducts, bile ducts, pancreatic acini, intestinal crypts, and testicular tubules were also GGT-positive. Small bands of positively stained stromal cells and GGT-positive histiocytes were seen in some tissues. Analysis of human fetal tissue shows that the developmental expression of GGT differs in humans and rodents. These findings form the basis for further work on GGT induction in tumors and the effect of GGT expression on the response of tumors to chemotherapy.

Amino Acid Sequence↗
PubMed1996

Microdose 14C-urea breath test offers diagnosis of Helicobacter pylori in 10 minutes.

OBJECTIVES: The urea breath test diagnoses Helicobacter pylori infection of the stomach by identifying the urease enzyme activity of the bacterium. In this "microdose" version of the test, 1 microCi 14C-urea is given orally in a capsule. Our objectives were: 1) to evaluate a microdose 14C-urea breath test capsule in a gastroenterology outpatient setting, 2) to determine the diagnostic ranges of the 14C-urea breath test for HP-positive and HP-negative patients, 3) to define the sensitivity and specificity of the test, and 4) to see whether breath sample results changed when they were mailed to a remote site for analysis. METHODS: In a prospective blinded study, we breath-tested 200 fasted patients before elective outpatient endoscopy. At endoscopy, two gastric biopsy samples were taken and were examined for curved organisms; a third biopsy specimen was evaluated with a rapid urease test (CLOtest). Breath samples were mailed in aluminized balloons to a testing laboratory. RESULTS: Using a single breath sample collected at 10 min, with > or = 200 dpm as positive, the breath test correctly classified 63 of 65 HP-positive patients (sensitivity 97%, CI 89-99%), and 128 of 135 HP-negative patients (specificity 95%, CI 90-98%). Radiation exposure from the test equated to natural background received in 1 day. No adverse events were caused by the breath test. CONCLUSIONS: The 14C-urea capsule breath test (PYtest) is a convenient noninvasive test for the detection of gastric H. pylori infection. Accuracy is equivalent to invasive methods such as histology. Results can be obtained within 15 min if a counting instrument is nearby, or breath samples can be mailed to a testing laboratory for analysis.

Adolescent↗
PubMed1996

Ovarian granulosa cell tumors with bizarre nuclei: an immunohistochemical analysis with fluorescence in situ hybridization documenting trisomy 12 in the bizarre component [corrected].

Granulosa cell tumors with bizarre nuclei (GCT-BN) are rare lesions with a prognosis apparently similar to that of conventional granulosa cell tumors (GCT-NOS). The immunohistochemical features of GCT-BN have not been described, and the exact nature of the bizarre nuclei (BN) is unclear. Thirteen GCT-BN were studied with antibodies to cytokeratin, vimentin, epithelial membrane antigen, muscle-specific actin, alpha smooth muscle actin, desmin, and S-100 protein. Six cases were also examined by fluorescence in situ hybridization for trisomy 12, a nonrandom chromosomal aberration found in a proportion of ovarian sex-cord stromal tumors. Histologically, 12 tumors (86%) contained BN areas interspersed with large areas of GCT-NOS. The remaining tumor contained only microscopic foci of GCT-NOS. Immunohistochemically, the tumors stained for vimentin (13 tumors), S-100 protein (11 tumors), muscle-specific actin (10 tumors), cytokeratin (eight tumors), alpha smooth muscle actin (eight tumors), and desmin (one tumor), but none stained for epithelial membrane antigen. Immunostaining results for the BN and GCT-NOS areas were concordant in eight (73%) of the 11 tumors in which both areas could be independently assessed. The remaining three tumors (27%) showed discordant results for only one of the eight markers used. In five patients, trisomy 12 was detected by fluorescence in situ hybridization in areas of BN but not in areas of GCT-NOS present in the same tumor. Trisomy 12 was also present in another BN tumor in which the foci of GCT-NOS were too small to be evaluated. We conclude that within GCT-BN, areas with BN are immunohistochemically similar to areas of GCT-NOS present in the same tumor. The finding of trisomy 12 in areas with BN but not GCT-NOS in the same tumor, however, suggests that cells with BN represent a genetically distinct clone of tumor cells arising within GCT-NOS.

Adolescent↗
PubMed1996

Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors.

Histological, immunological, and molecular methods have been used for detecting micrometastases from nonhematopoietic malignancies. Early studies utilizing cytological methods to identify circulating tumor cells demonstrated the uncertain significance of micrometastasis detection for predicting eventual recurrent disease. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. Studies using RT-PCR thus far indicate that test results may be negative in some patients with known metastatic disease, thereby raising doubts about the utility of the method for staging of disease. In this review, we survey the relevant literature and discuss the range of current applications of histological, immunological, and molecular methods for detecting micrometastases from solid tumors in blood, bone marrow, and lymph nodes and the progress toward determining the significance of micrometastasis detection.

Bone Marrow↗
PubMed1996

Immunohistochemical detection and gene amplification of cyclin D1 in mammary infiltrating ductal carcinoma.

The deregulation of cyclin D1 (BCL-1, PRAD1, CCND1) protein, normally synthesized in the G1 phase of the cell cycle, has been implicated in the pathogenesis of some malignant neoplasms, including invasive mammary carcinomas. We used rabbit polyclonal antibody 19 to detect cyclin D1 in 55 infiltrating ductal carcinomas and compared the findings to six important clinicopathologic parameters and cyclin D1 gene amplification. Nuclear immunoreactivity of variable intensity for cyclin D1 was present in 35% of the neoplasms, whereas immunoreactivity of normal mammary epithelial nuclei was absent. No significant correlations were observed between immunoreactivity and patient age, axillary lymph node status, estrogen receptors, progesterone receptors, histologic grade, or any of its three components. There was a correlation between cyclin D1 immunostaining and tumor size (P = 0.013). Fourteen of 15 tumors 2 cm or less were negative, whereas 7 of 12 neoplasms larger than 4 cm were immunopositive. Fifteen percent of the invasive carcinomas had cyclin D1 gene amplification. Of these eight tumors, six showed cyclin D1 immunoreactivity (P = 0.017). In this study, cyclin D1 was detected immunohistochemically in approximately one-third of infiltrating ductal carcinomas; approximately one-third of these had detectable cyclin D1 gene amplification. These results further implicate cyclin D1 in breast tumorigenesis and are additional evidence for the role of cell cycle regulatory proteins in invasive mammary carcinoma.

Adult↗
PubMed1995

Primary and metastatic high-grade carcinomas of the salivary glands: a cytologic-histologic correlation study of twenty cases.

We reviewed the clinical and fine-needle aspiration (FNA) findings in 20 patients with poorly differentiated carcinomas presenting initially as parotid or as submandibular masses. There were 11 primary tumors and nine metastatic malignancies in 14 males and six females ranging in age from 39 to 89 yr (median = 66). The tumor types included three primary carcinomas with oncocytic features, three additional cases of high-grade parotid carcinoma, one case of primary neuroendocrine carcinoma, two examples of malignant mixed tumor, one high-grade mucoepidermoid carcinoma, and a single example of malignant lymphoepithelial lesion. Six patients with metastatic carcinoma had previous diagnoses of malignancy. In the three remaining individuals, primary carcinomas of the lung (two cases), and an unknown primary site presented initially as parotid masses. Five examples of metastatic squamous cell carcinoma, one metastatic basal cell carcinoma, and two metastatic renal cell carcinomas were identified. One parotid lymphoepithelioma was interpreted cytologically as an atypical lymphoproliferative process suggestive of Hodgkin's disease. Nineteen cases (95%) were correctly classified as carcinoma at the time of FNA. High-grade carcinomas aspirated from the parotid may be primary, but are frequently metastatic to either the gland, or to an intraparotid lymph node. Our experience indicates that some metastatic carcinomas present at this site, without a previous history of malignancy. Distinguishing primary from metastatic lesions has important therapeutic implications.

Adult↗
PubMed1995

Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma.

The interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for invasive breast carcinoma was tested. Six surgical pathologists from four institutions independently evaluated histologic grade and each of its three components for 75 infiltrating ductal carcinomas. The number of slides per case ranged from one to nine (median 3). Pairwise kappa values for agreement ranged from moderate to substantial (0.43-0.74) for histologic grade. Generalized kappa values indicated substantial agreement for tubule formation (0.64), moderate agreement for mitotic count (0.52), and near moderate agreement for nuclear pleomorphism (0.40). Normalizing the mitotic counts per mm2 showed only slight improvement in agreement over the published range of mitotic counts for three different field areas. The results suggest that steps to discriminate between categories for nuclear pleomorphism would likely be of benefit for improving the interobserver reproducibility of histologic grade. Nevertheless, the Nottingham modification of the Bloom and Richardson grading system is recommended as a suitable scheme for evaluating invasive breast carcinomas in the routine clinical setting.

Breast Neoplasms↗
PubMed1995

Infrequent association of Epstein-Barr virus with CD30-positive anaplastic large cell lymphomas from American and Asian patients.

CD30 (Ki-1)-positive anaplastic large cell lymphoma (CD30+ ALCL) is a morphologically and immunophenotypically distinct subset of non-Hodgkin's lymphoma. Although the presence of Epstein-Barr virus (EBV) has been well documented in a significant proportion of cases of Hodgkin's disease, another CD30+ malignancy, few studies have examined the association of EBV with CD30+ ALCL. These latter studies have produced conflicting findings. To further investigate the existence of a putative association of EBV with CD30+ ALCL, and whether this association, if present, shows geographic variation, we examined 34 formalin-fixed, paraffin-embedded specimens from cases of CD30+ ALCL from the United States and Hong Kong. Immunophenotypically, 15 cases were of B lineage, 15 cases were of T lineage, one case expressed both B- and T-cell markers, and three were of null lineage. A highly sensitive in situ hybridization method was performed with use of an antisense oligonucleotide probe to the EBV-encoded RNA (EBER-1). EBV-RNA was identified in 3 of 14 CD30+ ALCL specimens from Hong Kong patients and in 1 of 20 from the American patients. The EBER-1 signal was present in all or virtually all of the tumor cell nuclei in the three EBV-RNA-positive CD30+ ALCL Hong Kong cases, but was only focally present in the single EBV-positive American case. The latent membrane protein-1 (LMP1) of EBV was identified in only one of the four positive cases, a Hong Kong case. Our results suggest that in contrast to Hodgkin's disease, EBV has no significant association with CD30+ ALCL.

Adolescent↗
PubMed1995

Proliferating cell nuclear antigen immunoreactivity and prognosis of gastrointestinal stromal tumors.

To determine the prognostic value of proliferating cell nuclear antigen (PCNA) immunoreactivity in gastrointestinal stromal tumors (GISTs), we analyzed 42 GISTs using the PC10 antibody. Thirty-nine GISTs with adequate follow-up were classified as non-aggressive or aggressive based exclusively on clinical behavior; a 2-year minimum follow-up was required for nonaggressive lesions. The percentage of PCNA-positive nuclei (%PCNA(+)) was significantly greater in colorectal GISTs compared with gastric tumors. No significant differences in %PCNA(+) were observed between gastric and small intestinal or small intestinal and colorectal tumors. The %PCNA(+) strongly correlated with mitotic rate, nuclear pleomorphism, and clinical behavior, whereas size and cellularity weakly correlated with %PCNA(+). Thirty-six GISTs could be classified as having low or high risk for aggressive clinical behavior based on a combination of tumor size, mitotic rate, and %PCNA(+). Twelve of 13 low-risk tumors were clinically nonaggressive, whereas 19 of 23 high-risk tumors were clinically aggressive. This correlation with clinical outcome was highly significant (P = 0.00002). Risk analysis by individual anatomical site also strongly correlated with clinical behavior for gastric (P = 0.0023) and small intestinal (P = 0.0056) tumors. There were too few colorectal GISTs with adequate follow-up and PCNA data for site-specific risk analysis. We conclude that tumor size, mitotic rate, and %PCNA(+) can be used as parameters to predict the clinical behavior of GISTs.

Cell Nucleus↗
PubMed1995

Medullary carcinoma of the breast: interobserver variability in histopathologic diagnosis.

To assess the interobserver reproducibility for the diagnosis of medullary carcinoma of the breast (MC), 53 previously diagnosed MCs were independently assessed by six observers for growth pattern, nuclear grade (NG), inflammation, tumor margin, intraductal component, and glandular features. Tumors were reclassified as MC, atypical MC, or infiltrating ductal carcinoma according to the histopathologic criteria of Ridolfi et al. (Cancer 40:1365, 1977), Wargotz and Silverberg (Hum Pathol 19:1340, 1988), and Pedersen et al. (Br J Cancer 63:591, 1991). NG was the most reproducible parameter, and tumor margin was the least, with consensus agreement by four of six observers for 49 (92%) and 26 (49%) of cases, respectively. Utilizing the histopathologic criteria proposed by Ridolfi et al., Wargotz and Silverberg, and Pedersen et al., consensus diagnoses were achieved in 37 cases (70%), 46 cases (87%), and 51 cases (96%), respectively. A consensus diagnosis of MC in all three systems was unassociated with tumor size, axillary lymph node status or overall survival (median follow-up: 89 mo). The consensus (or better) reclassification of 44/53 (83%), 35/53 (66%), and 27/53 (51%) previously diagnosed MC as atypical MC or infiltrating ductal carcinoma by the criteria of Ridolfi et al., Wargotz and Silverberg, and Pedersen et al., respectively, suggests that MC was previously over-diagnosed. While the scheme of Pedersen et al. is the most reproducible, additional follow-up information is necessary to determine the biological significance of this classification system. To minimize these difficulties in practice, pathologists should carefully adhere to published criteria and indicate the classification system utilized.

Adult↗
PubMed1995

Low frequency association of the t(2;5)(p23;q35) chromosomal translocation with CD30+ lymphomas from American and Asian patients. A reverse transcriptase-polymerase chain reaction study.

Although cytogenetic data suggest that the t(2;5)-(p23;q35) translocation occurs in many cases of CD30+ lymphomas, the exact frequency of this event is still unknown. To clarify this issue and its epidemiological characteristics, we examined 37 formalin-fixed, paraffin-embedded specimens of CD30+ lymphomas from the United States and Hong Kong by reverse transcriptase-polymerase chain reaction (RT-PCR) for the status of the NPM and ALK genes, which are typically juxtaposed by the t(2;5) translocation. Thirty-four cases were classified as anaplastic large cell lymphomas (ALCL), 2 cases as non-anaplastic large cell lymphomas (LCL), and 1 case as the small cell variant of CD30+ lymphoma. The t(2;5) translocation was detected in 6 cases (16%), including 3 of 18 American patients and 3 of 19 cases from Hong Kong. All cases had a 185-bp NPM RT-PCR product as detected by Southern blot analysis, indicating adequate preservation of mRNA. The 6 positive cases were among 4 of 34 adult lymphomas, as compared with 2 of 3 childhood cases. Five of 17 T-lineage cases were t(2;5)-positive, compared with 1 of 15 B-lineage cases and none of the 5 null-cell or mixed lineage cases. Our results therefore show that t(2;5) occurs at a low frequency among CD30+ lymphomas, at least in our adult-dominated series.

Adolescent↗
PubMed1995

Immunohistochemical staining and Southern blot hybridization for glutathione S-transferase pi in mammary infiltrating ductal carcinoma.

Glutathione S-transferase pi, a drug-detoxifying isoenzyme of potential prognostic value for subsets of patients with mammary cancer, was studied by immunohistochemistry and Southern blot analysis in 58 infiltrating ductal carcinomas. The results were compared with the findings of six important clinicopathologic parameters. Cytoplasmic immunoreactivity for glutathione S-transferase pi was absent in 40%, 1+ in 26%, 2+ in 15%, and 3+ in 19% of the cases. There were no significant correlations between the level of immunostaining and patient age, tumor size, axillary lymph node status, nuclear pleomorphism, or tubule formation, but there was a trend with mitotic count (P = 0.06). Immunoreactivity was associated with histologic grade (P = 0.02) and inversely correlated with estrogen (P = 0.006) and progesterone (P = 0.02) receptor content. Ten percent of the cases showed modest levels of glutathione S-transferase pi gene amplification, but no significant correlations were observed between glutathione S-transferase pi amplification and any of the clinicopathologic parameters or level of immunostaining. The results indicate that increased immunohistochemical staining for glutathione S-transferase pi occurs in high-grade, estrogen and progesterone receptor-negative neoplasms. As glutathione S-transferase pi gene amplification appears unassociated with immunopositivity, other mechanisms are responsible for the production of this isoenzyme in infiltrating ductal carcinomas.

Blotting, Southern↗