Background This study aimed to investigate the capability of an automated immunohistochemical (IHC) evaluation of hormonal receptor status in breast cancer patients compared to a well-validated quantitative reverse transcription–polymerase chain reaction (RT-qPCR) method.
Methods This study included 93 invasive breast carcinoma cases that had both standard IHC assay and Oncotype Dx assay results. The same paraffin blocks on which Oncotype Dx assay had been performed were selected. Estrogen receptor (ER) and progesterone receptor (PR) receptor status were evaluated through IHC stains using SP1 monoclonal antibody for ER, and 1E2 monoclonal antibody for PR. All ER and PR immunostained slides were scanned, and invasive tumor areas were marked. Using the QuantCenter image analyzer provided by 3DHISTECH, IHC staining of hormone receptors was measured and converted to histochemical scores (H scores). Pearson correlation coefficients were calculated between Oncotype Dx hormone receptor scores and H scores, and between Oncotype Dx scores and Allred scores.
Results H scores measured by an automated imaging system showed high concordance with RT-qPCR scores. ER concordance was 98.9% (92/93), and PR concordance was 91.4% (85/93). The correlation magnitude between automated H scores and RT-qPCR scores was high and comparable to those of Allred scores (for ER, 0.51 vs. 0.37 [p=.121], for PR, 0.70 vs. 0.72 [p=.39]).
Conclusions Automated H scores showed a high concordance with quantitative mRNA expression levels measured by RT-qPCR.
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Background Although both thyroid histology and serum concentrations of hormones are known to change with age, only a few reports exist on the relationship between the age-related structural and functional changes of the thyroid follicles in both mice and humans. Our objectives were to investigate age-related histological changes of the thyroid follicles and to determine whether these morphological changes were associated with the functional activity of the follicles.
Methods The thyroid glands of mice at 18 weeks and at 6, 15, and 30 months of age were histologically examined, and the serum levels of thyroid hormones were measured in 11-week-old and 20-month-old mice. Samples of human thyroid tissue from 10 women over 70 years old and 10 women between 30 and 50 years of age were analyzed in conjunction with serum thyroid hormone level.
Results The histological and functional changes observed in the thyroid follicles of aged mice and women were as follows: variable sizing and enlargement of the follicles; increased irregularity of follicles; Sanderson’s polsters in the wall of large follicles; a large thyroglobulin (Tg) globule or numerous small fragmented Tg globules in follicular lumens; oncocytic change in follicular cells; and markedly dilated follicles empty of colloid. Serum T3 levels in 20-month-old mice and humans were unremarkable.
Conclusions Thyroid follicles of aged mice and women show characteristic morphological changes, such as cystic atrophy, empty colloid, and Tg globules.
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Bcl-2 is a proto-oncogene initially described in follicular lymphoma, associated with chromosomal translocation(14;18).
Recent studies have shown the presence of Bcl-2 in nonhematolymphoid tissue, especially in hormonally responsive tissue. The endometrium is an attractive model for studying the hormone dependent regulation of Bcl-2 expression. We have studied the immunoreactivity of Bcl-2 oncoprotein in relation to the immunoreactivity of estrogen receptors(ER) and progesterone receptors(PR) by immunohistochemistry in 52 human endometrial carcinomas, according to nuclear grade. The results obtained are summarized as followings, 1) Immunohistochemical grade of Bcl-2 showed a significant inverse correlation with nuclear grade. 2) Immunohistochemical grades of ER and PR also showed a significant inverse correlation with nuclear grade, and were well correlated with each other. 3) Immunohistochemical grades of Bcl-2 and hormone receptors showed a strongly significant correlation. On the basis of the above results, we suggest that Bcl-2 expression may be under hormone dependent control and that it can be used in prognosis and choice of hormonal therapy in the presence of hormone receptor.
E-cadherin (E-CD), a Ca2+ -dependent adhesion molecule, plays a major role in the maintenance of intercellular junctions in normal epithelial cells in most organs.
Recently, a correlation has been observed between a loss of E-CD and increased invasiveness of neoplastic cells. In this study, E-CD expression in the breast carcinoma was investigated using monoclonal antibody, anti-E-CD by immunohistochemical method. Expression of E-CD were evaluated in 57 breast carcinomas and correlated with their tumor grade, lymph node involvement, and hormonal receptor status. Histological types included in this study were 54 invasive ductal carcinomas (IDCs) of otherwise not specified and 3 invasive lobular carcinomas. Cases of histologic grade I IDC were 6, grade II 30, and grade III 18. Of 54 IDCs 39 (72.2%) showed moderate to strong linear staining at the cell borders regardless of their histologic grade, status of lymph node metastasis, and status of hormone receptor.
Staining intensity of E-CD was reduced in 54 cases (83%) of IDC when compared with that of normal or benign breast lesions (P<0.01). All seven cases of intraductal carcinoma, which were included in 54 IDCs showed one or two grade reduced expression of E-CD than that of infiltrative lesions. Three invasive lobular carcinomas showed strong (1 case), moderate (1 case), and negative reactivity (1 case).
The data indicated that loss of E-CD expression is a crucial event in the development of breast carcinoma.
The current classification of pituitary adenomas is based on cell type, largely ascertained by immunohistochemistry and electron microscopy. In an application of immunohistochemistry, pathologists have some problems in judging the results. An immunostaining result does not always correspond with a serum hormone level. It is also difficult to determine the nature of a tumor when a few cells are positive. We performed the immunohistochemical stains on 34 pituitary adenomas using polyclonal antibodies to six pituitary hormones [PRL (prolactin), GH (growth hormone), ACTH (adrenocorticotropic hormone), FSH (follicle-stimulating hormone), LH (luteinizing hormone), TSH (thyroid-stimulating hormone)] and compared with serum hormone level. The serum hormone level was increased in 14 cases (41.2%) of PRL, 7 cases (20.6%) of PRL & GH, 6 pleurihormonal cases (17.6%), 4 nonfunctioning cases (11.8%), 2 cases (5.9%) of FSH, and 1 case (2.9%) of GH. The most common immunohistochemical type of pituitary adenoma was 10 prolactinoma cases (38.5%), followed by 7 pleurihormonal cases (26.9%), 4 null cell cases (15.4%), 3 cases of mixed PRL & GH (11.5%), 1 case of ACTH (3.8%) and 1 FSH & LH case (3.8%). The corresponding rates of the serum hormone level and immunostaining results were 94.1% in GH, 88.9% in TSH, 85.7% in LH, 82.4% in ACTH, 66.7% FSH, and 61.8% in PRL. In the immunostaining for FSH, 12 cases showed less than 5% positivity and most of them exhibited the normal serum hormone level. In conclusion, the most common elevated serum hormone and immunohistochemical type of pituitary adenoma was prolactinoma. The corresponding rate of the serum hormone level and immunostaining result was the highest in GH cell adenoma and was the lowest in prolactinoma. The cells showing less than 5% positivity seem to be entrapped normal cells.
Breast cancer is the most common malignancy of women in industrialized countries and the third in Korean women.
There have been a lot of studies on biologic behaviors as well as on the prognostic factors of the breast cancer. In this study, the expression of hormone receptors (estrogen receptor ; ER, progesterone receptor ; PR, and androgen receptor ; AR), bcl-2 and Rb proteins were immunostained on 60 infiltrating ductal carcinomas of the breast. The results were evaluated in relation with the age, histologic grade, tumor size, and status of lymph node metastasis. The expression of ER and PR had a significant inverse correlation with the histologic grade (p<0.001). The expression of AR was significantly correlated with the expression of ER (p=0.039) and PR (p=0.009), but not with other factors such as age, histologic grade, tumor size, and status of lymph node metastasis. There was no relationship between bcl-2 protein expresssion and other prognostic factors, except with the expression of ER. Rb protein expression had a significant positive relationship with PR (p=0.05) and the degree of positivity was correlated with histologic grade (p=0.002). In conclusion, this result suggests that expression of AR is well correlated with ER and PR. bcl-2 has no prognostic value. The significance of Rb protein expression remained to be studied.
In 41 cases of breast cancers, the aneuploidy measured by Image Analyzer was compared with that of flow cytometric analysis, and estrogen and progesterone receptor(ER/PR) and Her-2/neu oncoprotein were immunohistochemically stained and measured by Image Analyzer. In ER/PR, the positive nuclear area(PNA, %) was measured, and in Her-2/neu, the content of oncoprotein was expressed as pg/cell. To assess the usefulness of these parameters as a prognostic factor, the author evaluated the results in relation with tumor size, nuclear grade and lymph node metastasis. The obtained results are summarized as follows: 1) The detection rate (90%) of aneuploidy by image analysis was higher than that (70%) of flow cytometric analysis. The concordance rate of both method was 80%. 2) The positivity of ER was 73% and PR was 34%, and the high PNA of ER and PR was related with high nuclear grade. There was an inverse correlation of the ER PNA with tumor size and PR PNA with negative lymph node. 3) Her-2/neu oncoprotein overexpression was found in only 2 cases and another two showed borderline overexpression. All four cases had DNA tetraploidy. From the above results, it was concluded that the image analyzer could be used in DNA analysis and in quantitation of immunostained ER/PR and Her-2/neu oncoprotein, providing the important information in the management of the breast cancer patients.