Occult breast lesions and aspiration biopsy: a new challenge.
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Biomedical subjects
Publications and source records attributed to S Masood.
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Although Hürthle cell tumors are considered to be variants of follicular neoplasms, they have distinct cytologic and behavioral characteristics. To elucidate the basis for these differences, the expression of 5 oncogenes and growth factors (Pan-ras, N-myc, transforming growth factor-alpha [TGF-alpha], transforming growth factor-beta [TGF-beta], and insulin-like growth factor 1 [IGF-1]) was compared between 12 follicular carcinomas and 8 Hürthle cell carcinomas by immunocytochemistry. The percentage of follicular carcinomas and Hürthle cell carcinomas that stained positively for the different oncogenes was as follows and respectively: Pan-ras 8% versus 63%; TGF-alpha 17% versus 63%; TGF-beta 25% versus 88%; IGF-1 17% versus 88%; and N-myc 17% versus 100%. All these differences were highly significant by the chi 2 test. This difference in the expression of oncogenes between Hürthle cell carcinomas and follicular carcinomas suggests that these two tumors could, in fact, represent separate entities.
PURPOSE AND METHODS: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GST pi also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GST pi was developed to examine the possible relationship between GST pi expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. RESULTS: A strong inverse correlation between GST pi expression and ER (two-sided P [P2] = .002) and PR status (P2 = .023) was found in our study of 189 patients with primary breast cancer. GST pi expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GST pi expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GST pi expression was divided into categories of negative (no GST pi-positive tumor cells), intermediate (1% to 70% GST pi-positive tumor cells), and high (> 70% GST pi-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P2 = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P2 = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%, and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GST pi expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. CONCLUSION: GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.
DCIS is an early localized stage of mammary malignancy that has an especially favorable prognosis with appropriate management. It seems to be a direct precursor to invasive carcinoma of the breast and has the same therapeutic options. There are still many outstanding issues to be resolved before the intriguing potential of this disease can be fully realized. Any physician involved in the management of diseases of the breast must be committed to a thorough understanding of all aspects of the biologic factors of this entity, so as to be able to rationally provide appropriate advice and treatment. Ongoing investigations should advance the knowledge and experience with this disease in future years.
Previous reports have shown that estrogen and progesterone receptors (ER and PgR) are detectable in neoplastic and non-neoplastic thyroid tissues using a variety of techniques. However, differences in relative expression of ER and PgR according to tumor type have not been emphasized. To determine whether such differences occur and to assess clinicopathologic correlations, we have evaluated ER and PgR expression in sections of 64 thyroid lesions stained by indirect immunoperoxidase. The lesions studied included 39 papillary carcinomas, 3 follicular adenomas, 2 follicular carcinomas, 15 Hürthle cell tumors, 3 medullary carcinomas, and 2 multinodular goiters. Immunostaining was achieved using monoclonal antibodies H222 to ER and JZB39 to PgR. Additionally, the monoclonal antibodies D75p3 to ER and mPRI to PgR were also used in some cases. Overall, ER and/orPgR were detected in 26 of 64 lesions (40%) using any of the above antibodies. ER was identified in eight of 64 (12.5%) tumors that were all papillary carcinomas. No staining for ER was seen in follicular neoplasms, Hürthle cell tumors, or medullary carcinomas. PgR staining was present in 13 of 39 (33%) papillary carcinomas, 8 of 15 (53%) Hürthle cell tumors, 2 of 7 (28%) follicular tumors, and in none of 3 medullary carcinomas. Non-neoplastic thyroid tissue was negative for ER and PgR in all but one case in which weak staining for PgR was present adjacent to a follicular adenoma. There were no correlations between ER and/or PgR staining and age, gender, tumor size, presence of capsular or vascular invasion, or lymph node status in any tumor.(ABSTRACT TRUNCATED AT 250 WORDS)
The role of mammography as an effective means of early detection of breast cancer is well established. Needle localization of occult tumors under mammographic guidance has become the principle method of sampling impalpable breast lesions. As a result, the number of clinically inapparent breast carcinomas sampled has increased rapidly. Under these circumstances, as a result of the size and the nature of these "early carcinomas," it may not be possible to assess the hormone receptor expression of these tumors by conventional biochemical assay and/or immunocytochemical analysis. To determine the usefulness of imprint preparation for detecting hormone receptors, 214 examples of primary, recurrent, and metastatic breast cancers were studied. Immunostaining of imprint preparations with monoclonal antibodies against the estrogen (H222SPy) and progesterone receptors (KD68) showed a high degree of concordance with immunocytochemical assay and biochemical analysis done on frozen tissue of the same tumors. This technique can be done easily and is well suited for tumors that are too small and/or ill defined to permit separate sampling for hormone receptor analysis.
One hundred patients with node-negative breast cancer were examined to analyze the influence of tumor size, nuclear grade, and DNA content determined by flow cytometry on overall survival. Patients with diploid cancers lived significantly longer than those with aneuploid cancers (126 +/- 8 vs 80 +/- 11 months). Patients with an S-phase fraction less than 10% lived significantly longer than those with S-phase fractions 10% or greater (122 +/- 8 vs 85 +/- 10 months). Tumor size had the major impact on survival, and multivariate analysis of variance by the Cox proportional hazards model showed the greatest effect on prognosis. Tumor grade did not significantly influence overall survival.
An immunocytochemical assay utilizing specific monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PgR) has been shown to be highly reliable for the detection of hormone receptors in hormone sensitive tumors. To assess the usefulness of this technique in malignant effusions, CytospinR (Shandon, Inc., Pittsburgh, PA 15275), preparations of 41 pleural and ascitic fluid were studied. The findings from the malignant cells employing estrogen and progesterone receptor immunocytochemical assay were compared with the results obtained from primary tumors by biochemical (dextran-coated charcoal) assay. The results agreed in 88% for ER and 83% for PgR. This study supports the potential value of cytochemical technique in detection of hormone receptors in malignant effusions. Assessment of hormone receptors in malignant effusions may be of clinical significance, particularly in situations where the hormone receptor status of the original tumor is not known. This information may also have some diagnostic and therapeutic importance in assessment of patients presenting with metastatic tumors of unknown origin.
Fine-needle aspiration biopsy is a well-established procedure in the detection of various neoplastic processes. However, there are only limited reports on the efficacy of this technique in nonneoplastic conditions. In this study, fine-needle aspiration cytology findings of bone and soft tissue lesions in 11 patients with tuberculosis are reported. Spine, scapula, chest wall, flank areas, tibia, ring, and index fingers were the sites of fine-needle aspiration biopsies. The age of the patients ranged from 21 to 65 years. Granulomatous reaction with or without caseation necrosis was seen in 73%. The aspirated material was acellular or predominantly composed of necrotic material and inflammatory infiltrates in 27%. Acid-fast bacilli (AFB) could be demonstrated in 64%. Culture for Mycobacterium tuberculosis was positive in 83%. This study supports previous suggestions that fine-needle aspiration biopsy is a simple alternative to open biopsy for the diagnosis of TB of bone and soft tissue lesions.
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Oncogene expression has been found to be a potential marker for aggressive biologic behavior in certain tumors. We studied 21 follicular adenomas and 20 follicular carcinomas by immunocytochemistry utilizing specific monoclonal antibodies against HER-2/neu and c-myc oncogenes. Survival data were obtained from our institution's tumor registry. No expression of the HER-2/neu oncogene was found in the specimens studied. Cytoplasmic staining for c-myc was observed in 3 of 21 adenomas (14%) and 9 of 20 (45%) carcinomas (p < 0.05). The incidence of local, regional, and distant metastases was not significantly different in c-myc (+) and c-myc (-) patients. The c-myc oncogene is expressed more often in malignant than in benign follicular neoplasms of the thyroid, but its expression does not appear to be a good prognostic indicator.
The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.
Many hepatic adenomas have been demonstrated to have a clear relationship with oral contraceptive use, and it is presumed that there may be hormone receptors within the cytoplasm or nucleus of adenoma cells that mediate tumor growth in response to hormonal stimulation. Only a small number of examples of benign hepatic tumors have been analyzed for the presence of estrogen and progesterone receptors, and there has been a lack of consensus with regard to the findings. All previous studies have determined receptor levels by biochemical methods. In a retrospective study, we employed specific monoclonal antibodies against estrogen and progesterone receptors in 10 benign paraffin-embedded hepatic lesions: five examples of hepatic adenoma and five examples of focal nodular hyperplasia. All patients were female, except for one male with adenoma and one male with focal nodular hyperplasia. No patient had received tamoxifen citrate or any other form of hormonal therapy for their hepatic lesion. Positive controls included benign and malignant breast tissue. No positive staining was seen in hepatic adenoma, focal nodular hyperplasia, or normal adjacent liver parenchyma. Intense positive staining was seen in all positive control tissues. This negative result with the use of specific monoclonal antibodies in an established immunohistochemical method for analysis of estrogen and progesterone receptors does not exclude the presence of these receptors in benign hepatic lesions, but does suggest that, if present, they occur in much smaller amounts than in benign and malignant breast tissue. The presence of hormone receptors in benign hepatic tumors deserves further study.
Fine-needle aspiration biopsy (FNAB) is considered a valid diagnostic procedure in management of patients with breast lesions. It is also important to differentiate benign nonproliferative change from proliferative breast changes, since the risk of development of breast carcinoma in patients with atypical hyperplasia is 4-5 times that of general population. Therefore, the recognition of proliferative breast disease with atypia significantly impacts on the patient's subsequent management. To assess the feasibility of a cytologic grading system to further characterize benign breast lesions, cytologic preparation of 87 mammographically guided FNABs were studied. Cellular aspirates were evaluated for the cellular arrangement, the degree of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. Values ranging from 1 to 4 were assigned to each cytologic criterion, and a score based on the sum of the individual values was calculated for each case. The minimum score attainable was thus 6. In our chosen criteria cytologic diagnosis of nonproliferative disease was entertained when the total score ranged from 6 to 10. Proliferative disease without atypia was diagnosed with a total score ranging from 11 to 14. Atypical hyperplasia was reported when the total score ranged from 15 to 18. A cytologic diagnosis of malignancy was entertained when the total score ranged from 19 to 24. The cytologic diagnosis was then compared to the reported histologic diagnosis from the excisional biopsies and the data were statistically analysed. A high degree of concordance was found between the cytologic findings and the histologic diagnosis. This study suggests that it is possible to apply a cytologic grading system to further subclassify benign breast disease and distinguish these forms from neoplastic lesions.
One hundred cases of invasive breast carcinoma were studied using the commercially available monoclonal antibody Anti-Human Tumor-Associated Glycoprotein-72 (MAb B72.3, Biomedical Technologies Inc, Stoughton, MA) prediluted at 8.5 micrograms/mL. Forty-three cases displayed positive reactivity with this antibody. Intensity and distribution of positive staining varied among the tumor cells. Twenty-two cases had 1% or less reactive cells, while eight cases contained 40% or more positive tumor cells. Apical cell membrane and diffuse cytoplasmic staining were present. In fifteen cases intracytoplasmic lumina and extra-cellular secretory material were highlighted by positive staining. Thirty-five cases had benign breast tissue adjacent to the tumor. Benign ductal and lobular epithelial cells were nonreactive except for two cases in which small foci of apocrine metaplasia were positive. Reactivity with MAb B72.3 was not dependent upon histologic grade, nuclear grade, nodal status, or patient age. Excluding the lower number of positively stained cases, our findings were similar to other MAb B72.3 investigations. The number of positively stained cases and the intensity of the positivity were increased by using MAb B72.3 at 5.0 micrograms/mL with overnight incubation, or by using MAb B72.3 at 40.0 micrograms/mL with 2 hours of incubation. Our findings confirm that MAb B72.3 shows reliable reactivity with breast carcinoma that is sensitive to antibody concentration and incubation time without loss of specificity for tumor cells. Our results are also consistent with the view that MAb B72.3 probably detects epithelial membrane-related antigens in breast carcinoma, as do several other antibodies.
Estrogen and progesterone receptors were studied in fine-needle aspiration biopsy specimens of 56 patients with primary, recurrent, or metastatic breast carcinoma. The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesterone hemisuccinate bovine serum albumin tetramethyl rhodamine isothiocyanate (TMRITC-BSA progesterone), were used in the fluorescent cytochemical method. The findings obtained from the aspirated cells with the use of the fluorescent cytochemical technique were compared with results obtained from the cell population of the same tumor after removal with the use of both the fluorescent cytochemical technique and the biochemical dextran-coated charcoal (DCC) assay. For the needle aspirates, there was 89% concordance for estrogen receptor and 86% concordance for progesterone receptor between biochemical and cytochemical results. A high degree of correlation was also demonstrated between fine-needle aspirates and imprint preparations with the use of the cytochemical technique. This study suggests that the fluorescent cytochemical technique is an effective tool in assessment of estrogen and progesterone receptor content in fine-needle aspirates of primary and metastatic breast cancer. The fluorescent cytochemical technique can be performed easily at community hospitals and is well suited for specimens of insufficient size for biochemical assay.
Breast cancer specimens from 116 patients were assayed for the presence of progesterone receptor (PR), with the use of a highly specific monoclonal antibody and the peroxidase-antiperoxidase technique on cryostat and permanent sections. Results were compared with those obtained by the conventional PR determination by dextran-coated charcoal (DCC) assay; they were in concordance in 90% of cryostat sections and 85% of paraffin-embedded tissue. The sensitivity and specificity of the PR immunocytochemical assay (PR-ICA) were 91% and 89% for frozen sections and 83% and 89% for permanent sections, respectively. The immunostained slides also were evaluated for several semiquantitative features, including staining intensity, heterogeneity of staining, and the proportion of positive tumor cells. A statistically significant correlation was found between the percentage of tumor cells stained with the PR immunocytochemical technique and the PR-cytosol levels (P less than 0.05). These results suggest that the PR-ICA is an effective tool in the evaluation of PR content in breast cancer and can be applied in paraffin as well as frozen sections. This technique provides excellent morphologic detail, as well as tissue localization for PR. It also offers an alternative for assessment of PR when fresh tissue is not available for conventional hormone receptor analysis. The immunocytochemical assay can be performed easily at community hospitals. Because it requires only a small amount of tissue, PR-ICA is an ideal method for analyzing specimens of insufficient size for the DCC assay. This technique also is suited to the evaluation of fine-needle aspiration biopsy specimens.