Journal of Pathology and Translational Medicine

Original Articles

Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects: Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk; J Pathol Transl Med. 2019;53(4):236-243. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.21

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Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

Citations

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Rare non-serous fallopian tube cancers: institutional experience and literature review
Dmitrii Sumtsov, Georgyi Sumtsov, Nataliia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Nataliia Kalashnik, Svitlana Smiian, Igor Gladchuk
Wiener Medizinische Wochenschrift.2024; 174(9-10): 199. CrossRef
UŞAQLIQ BORULARININ BİRİNCİLİ XƏRÇƏNGİ: DİAQNOSTİKASI VƏ MÜALİCƏSİNİN NƏTİCƏLƏRİ
D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
Azerbaijan Medical Journal.2023; (4): 75. CrossRef
FEATURES OF ENDOMETRIUM STRUCTURE IN ALCOHOL-ABUSING HIV-INFECTED INDIVIDUALS
M. Lytvynenko
Inter Collegas.2021; 8(1): 52. CrossRef
Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos)
Mandy Womble, Megan E. Schreeg, Allison Hoch, Enoch B. de Souza Meira, Derek Foster, Christopher Premanandan, Tatiane T. Negrão Watanabe
Journal of Comparative Pathology.2021; 189: 52. CrossRef
Problems of primary fallopian tube cancer diagnostics during and after surgery
D.G. Sumtsov, I.Z. Gladchuk, G.O. Sumtsov, N.I. Hyriavenko, M.S. Lyndin, V.V. Sikora, V.M. Zaporozhan
REPRODUCTIVE ENDOCRINOLOGY.2021; (59): 66. CrossRef

Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics: Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim; J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.16

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Abstract PDF

Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT.

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Uterine carcinosarcomas: A case series of 9 cases from a low-income country
Boubacar Efared, Halidou Hamadou Koura, Aïchatou Balaraba Abani Bako, Idrissa Boubacar, Habiba Salifou Boureima, Garba Mahamadou, Hassan Nouhou
Medicine.2024; 103(40): e39773. CrossRef
Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential
Mohan Shankar Gopinatha Pillai, Pallab Shaw, Arpan Dey Bhowmik, Resham Bhattacharya, Geeta Rao, Shailendra Kumar Dhar Dwivedi
The FASEB Journal.2024;[Epub] CrossRef
Tamoxifen/toremifene

Reactions Weekly.2019; 1758(1): 330. CrossRef
Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
Susanna Leskela, Belen Pérez-Mies, Juan Manuel Rosa-Rosa, Eva Cristobal, Michele Biscuola, María L. Palacios-Berraquero, SuFey Ong, Xavier Matias-Guiu Guia, José Palacios
Cancers.2019; 11(7): 964. CrossRef

Pathologic Characteristics of Ovarian Hemorrhagic Polycyst in Estrogen Receptor-alpha (ERalpha) Knockout Mice and Roles of ERalpha in Hemorrhagic Polycyst.: Hyun Jin Son, Joo Heon Kim, Hye Kyung Lee, Mee Ja Park, Dong Wook Kang, Che Myong Ko; Korean J Pathol. 2010;44(4):376-383.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.376

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Abstract PDF: BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERalphaKO) mice display several pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERalphaKO mice using a CreloxP approach and intra-ovarian ERalpha function as regulating key aspects of PCOS.
METHODS
ERalphaKO mice, which were deficient in exon 3 of the ERalpha gene, were used. Immunohistochemical studies were done on ovaries of control and ERalphaKO mice using antibodies specific to ERalpha, ERbeta, inhibin-alpha, and alpha-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B.
RESULTS
All ovaries of ERalphaKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERalphaKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of alpha-SMA.
CONCLUSIONS
ERalphaKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERalpha is the functional key to the pathogenesis of PCOS.

An Immunohistochemical Study of the Relationships between Estrogen and Progesterone Receptors and Proliferating Cell Nuclear Antigen in Endometrial Hyperplasia and Adenocarcinoma.: Seol Mi Park, Hye Kyoung Yoon, Jong Eun Joo; Korean J Pathol. 1996;30(1):15-22.

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Abstract PDF: Estrogen and progesterone receptors exist in the epithelial and stromal cells of the endometrium. Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions of estrogen and progesterone in epithelial and stromal cells. This study was performed to evaluate the differences estrogen and progesterone receptor(ER/PR) expression in the epithelial and stromal cells of endometrial hyperplasias and adenocarcinomas using immunohistochemical methods. Immunohistochemical analysis of proliferating cell nuclear antigen(PCNA) was done to evaluate a possible correlation between PCNA and hormone receptor expression. Evaluation was based on samples from 31 simple hyperplasias, 30 complex hyperplasias, and 32 adenocarcinomas. The immunohistochemical expression of ER, PR and PCNA in epithelial and stromal cells were examined according to a scoring system based on the percentage of positive cells and the staining intensity. The results were as follows; 1) The expression of ER and PR in epithelial cells showed a graded, significant decreases in simple hyperplasia, complex hyperplasia and endometrial carcinoma, in that order(ER: P=0.008, PR: P= 0.026). 2) PR expression in the stromal cells showed a significant decrease between hyperplasia and adenocarcinoma(P=0.003). The difference in ER expression was not significant. 3) In stromal cells, the decrease in PR expression was more prominent than the decrease in ER expression when complex hyperplasia was compared to simple hyperplasia. 4) The PCNA expression in simple and complex hyperplasia and adenocarcinoma was not higher than the expression of PCNA in nomal proliferative endometrium. There was no significant difference in PCNA expression between simple and complex hyperplasia and adenocarcinoma(P=0.073). 5) A negative correlation between PCNA and ER/PR expression was not demonstrated in simple and complex hyperplasia, or in adenocarcinoma. Endometrial hyperplasia and adenocarcinoma are probably related to a paracrine action of estrogen and progesterone in epithelial and stromal cells. A progressive loss of PR expression in stromal cells may induce abnormal proliferation of endometrium due to a disrupted hormonal balance.

Clinical Value of Demonstration of Estrogen and Progesterone Receptors using Paraffin Wax Sections in Breast Carcinoma.: Hye Kyung Ahn, Yun Jung Kim, Young Euy Park; Korean J Pathol. 1996;30(2):89-93.

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Abstract PDF: This study aimed at assessing the usefulness of paraffin wax sections for demonstration of ER(estrogen receptor) and PR(progesterone receptor), using brief microwave processing rather than proteolytic predigestion. The receptor status of a breast cancer is often into consideration when planning treatment nowadays. As biochemical receptor assays require large amount of fresh tumor tissue and are not always available for all tumors, pathologists are now increasingly asked to provide a service for the assessment of the receptor status in tissue routine sections. Until recently, immunohistochemical demonstration of receptors was used in frozen sections. Therefore, routinely processed paraffin wax sections of 25 cases of breast carcinoma with known ER and PR concentrations, estimated by the standard DCC(dextran-coated charcoal) biochemical assay, were examined using the ABC immunoperoxidase technique. The results were assessed semiquantitably, using a five grade scoring system. Of the 25 cases examined, with DCC cutoff point being <10 fmol,71% and 75% in positivity of each ER, PR receptor is concordant. Statistic analysis demonstrates high relationship between scoring system of IH method and DCC value in ER (R=0.6061, p=0.001) and PR (R=0.5832, p=0.001). The IH method can provide easily assessed reliable positive information about ER, PR status of breast carcinoma using routinely processed paraffin wax sections.

Immunohistochemical Analysis of Estrogen Receptors and Progesterone Receptors in Leiomyoma of Uterus Compared with PCNA Index.: Jung Ran Kim; Korean J Pathol. 1996;30(2):140-149.

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Abstract PDF: Estrogen receptor(ER) and progesterone receptor(PR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in leiomyomas and myometrium from same patients from 38 women in various stages of the menstrual cycle, menopause and pregnancy. Two postpartum uteri are also included. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution, and the results were compared with those of PCNA index. In all samples, ER and PR localized within the nuclei of target cells. The histochemical score of ER in leiomyoma was significantly greater than that found in myometrium. But ER in leiomyoma was expressed in cyclic fashion(r=0.45, P=0.006), like as in myometrium, throughout the menstrual cycle, paralleled by a concomitant, though delayed. In contrast, PR content constantly maintained in myometrium and leiomyoma throughout menstrual cycle, and there was no significant difference between them. However, leiomyoma and myometrium of pregnancy showed a significant reduction in the amount of ER and PR localized. PCNA index in leiomyoma(14.9+/-24.4) was also significantly higher than that found in myometrium(2.1+/-3.3). The index declined throughout the secretory phase. The leiomyoma had increased PCNA index during pregnancy, while the increasing rate in leiomyoma was lower than that of myometrium. The growth potential of leiomyomas is appearently higher than that of myometrium under the high progesterone level. The most of neoplasm with high PCNA index(10 above) contained absolute or relative abundant PR or ER content. Alteration of receptor content may be an important mechanism in steroid dependent growth of leiomyoma and may provide information useful in the clinical management of this neoplastic disorder.

Analysis of Estrogen and Progesterone Receptors in Breast Carcinoma: Comparison of immunocytochemical assay with biochemical dextran-coated charcoal assay.: Ill Hyang Ko, Kyeong Mee Park; Korean J Pathol. 1996;30(3):228-237.

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Abstract PDF: Estrogen receptor(ER) is a soluble form of hormone receptor protein which is located in the nucleus and cytoplasm of a cell is found in 60% of cases of the cells of breast carcinoma. Fifty to sixty percent of ER positive breast carcinoma responds to antihormone therapy wheres the response rate is only 5% in ER negative tumors. Currently, the ER assay has become a standard index in the management and prediction of the prognosis of advanced breast carcinoma. Semiquantitative biochemical assay, dextran-coated charcol(DCC) assay, to measure ER from fresh tissue was first developed by Korenman in 1970 using isotope-labled ertradiol, has been widely utilized. In 1978, Kurzon newly developed immunocytochemical assay(ICA) employing monoclonal antibody against those hormone receptors to detect intracellular localization of ER and progesterone receptor (PR). The results of the assay have been reported by many investigators thereafter. The purpose of this study was to evaluate the hormonal receptors with a monoclonal antibody using an immunoperoxidase procedure to detect both estrogen and progesterone receptors (ER-immunocytochemical assay:ER-ICA and PR-immunocytochemical assay:PR-ICA) in 59 cases of paraffin embedded sections from formalin-fixed and routinely processed breast carcinoma tissue. Concomitantly, fine-needle aspiration biopsy cytology of the breast cancer from 29 women were assayed for ER/PR receptors. Results were compared with quantitative biochemical values determined from dextran-coated charcoal(DCC) assay on the fresh tumor tissue obtained subsequently from the surgery. ER-ICA showed positive result in 22 out of 36 DCC-positive cases(sensitivity, 61.1%) and negative in 23 out of 23 DCC-negative cases (specificity, 100.0%). PR-ICA was positive in 33 out of 35 DCC-positive cases(sensitivity, 94.3%) and negative in 16 out of 24 DCC-negative cases(specificity, 66.7%). The value of ER-ICA or PR-ICA positivity were roughly correlated with the concentration of ER/PR receptors analyzed by DCC method. The results of both methods were correlated with the nuclear grade of the tumor(ICA:p=0.002, DCC: p=0.015) but were not correlated with histologic grade(ICA: p=0.323, DCC: p=0.0164). ER-ICA positivity was correlated with lower incidence of axillary node metastasis (p=0.021) but no significant correlation between PR-ICA positivity and node metastasis(p=0.171). Both ER/PR-ICA positivity were not correlated with age(p=0.924) and tumor size(p=0.663). The score of ICA particularly ER was proportional to DCC level(ER: r=0.5, p=0.000, PR: r=0.2, p=0.000). ICA concordance with DCC of ER and PR were 76.3% and 83.1%, respectively. The concordance of PR-ICA and DCC was proportional but was statistically less significant. In aspiration biopsy cytology the concordance of ER/PR-ICA and DCC were 72.4% and 65.5%, respectively. Immunocytochemical staining to identify ER/PR receptors from the tissue of breast carcinoma would be tested as a mean to substitute for the conventional DCC method.

Expression of p53, bcl-2 Proteins and Estrogen Receptors in Human Breast Cancer.: Hee Kyung Chang, Choong Han Lee, Man Ha Huh; Korean J Pathol. 1996;30(8):662-670.

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Abstract PDF: In 56 breast cancer tissues (infiltrating ductal carcinoma) with a clinical follow-up period of more than 5 years, positivity of estrogen receptor(ER) by enzyme immunoassay and expressions of bcl-2 and p53 oncoproteins by immunohistochemistry were evaluated. The purposes of this study were to determine prevalence of bcl-2 and p53 in breast cancer, the interrelationship between expression of the proteins and estrogen receptor, correlation between histologic grade and the expression of the tumor-related oncogenes, and to explore the biologic bahavior of breast cancer (lymph node metastasis, recurrence rate, and survival) via expression of bcl-2 and p53. Twelve of 56 (21.4%) carcinomas were bcl-2 positive, and seventeen (30.4%) were p53- positive. Eleven of 12 bcl-2 positive tumors (91.7%) were ER-positive, and bcl-2 expression was significantly associated with ER-positivity(P=0.043). Seven of 36 ER-positive tumors (12.5%) were p53 positive, and p53 expression was inversely associated with ER-positivity(P=0.006) significantly. The bcl-2 protein expression showed a significant relationship to low histologic grade of tumor (P=0.0002), and an almost significant relationship to lower recurrence rate (P=0.09). The p53 protein expression showed a significant relationship to high histologic grade of tumor (P=0.002) and an almost significant relationship to lymph node metastasis (P=0.09). Also an almost inverse relationship between bcl-2 and p53 was demonstrated (P=0.057). The bcl-2 expression had a tendency to be associated with longer patient survival(P= 0.09), but p53 immunoreaction was found not to be associated with shorter patient survival(P=0.16). These results provide further evidence that higher incidence of bcl-2 expression is correlated with higher incidence of ER and lower grade of tumor, while p53 expression is correlated with lower incidence of ER and higher grade of tumor. In conclusion, although the biologic function of bcl-2 protein is not yet well understood in breast cancer, our results suggest that bcl-2 and p53 oncoproteins might play significant roles in estrogen receptor and development of breast cancer. But their prognostic significance could not be determined; our results are 'not significant' but 'almost significant'. Thus, contribution of bcl-2 and p53 immunohistochemical phenotyping of breast cancer with ER to the clinical management need verification in larger series.

Cyclin D1 Expression in 101 Cases of Breast Carcinoma.: Duck Hwan Kim, Eun Sook Nam, Hyung Sik Shin, Jin Woo Ryu, Jai Hyang Go, Young Lyun Oh, Sang Yong Song, Dae Shick Kim, Min Chul Lee; Korean J Pathol. 1998;32(4):266-272.

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Abstract PDF: Cyclin D1, a cell cycle regulator essential for G1 phase progression, is a candidate proto-oncogene implicated in pathogenesis of several human carcinomas including breast carcinoma. We studied the cyclin D1 expression in 101 cases of primary breast carcinoma tissues. The overexpression of cyclin D1 was immunohistochemically demonstrated in 34 (37.8%) of 90 cases of invasive breast carcinoma. Positive cyclin D1 staining was seen in 32 of 79 invasive ductal carcinomas, and 2 of 3 mucinous carcinomas. All 5 medullary carcinomas, 2 invasive lobular carcinomas, and 1 metaplastic carcinoma were negative. Cyclin D1 overexpression was observed in 9 of 11 ductal carcinoma in situ (DCIS). Normal epithelial components, either ductal or lobular, were not immunoreactive for cyclin D1. No significant correlations were observed between cyclin D1 immunoreactivity and other parameters including tumor size, clinical stage, nuclear or histologic grades, lymphatic or angioinvasion, lymph node metastasis, and immunohistochemical status of progesterone receptor, p53 and c-erbB-2. The overexpression of cyclin D1 was positively correlated with estrogen receptor status (p=0.025). Based on our results, the cyclin D1 protein aberration may play a role in tumorigenesis of breast carcinoma, but does not seem to have prognostic value in invasive breast carcinoma without hormonal treatment.

Immunohistochemical Expression of p53 Protein, Estrogen and Progesterone Receptor in Soft Tissue Leiomyosarcoma and Its Significance.: Byung Heon Kim; Korean J Pathol. 1998;32(11):1015-1024.

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Abstract: This study was carried out to evaluate the expressions of the p53 protein, the estrogen receptor (ER) and the progesterone receptor (PR), as well as the relationship between their expressions and clinicopathologic prognostic factors with storage duration of a paraffin block, and correlation between the p53 protein, the ER and the PR expressions in 29 cases of leiomyosarcoma of soft tissue. The expressions of the p53 protein, the ER and the PR were semiquantiatively analyzed in paraffin sections by the immunohistochemical method out of 29 cases the p53 protein, ER and PR were expressed in 9 (31.0%), 2 (6.9%) and 5 (17.2%), respectively. The expression of the p53 protein was not significantly associated with sex, age, anatomic site, tumor size, tumor depth, histological differentiation or mitotic rate (p>0.05), but statistically correlated to storage duration of a paraffin block (p=0.028). There was no significant relationship between the expression of the ER and all the clinocopathological prognostic factors with storage duration of a paraffin block (p>0.05). The expression of the PR was related to the histological differentiation (p=0.02), but not related to other clinicopathological prognostic parameters and storage duration of a paraffin block (p>0.05). The expression of the p53 protein and the PR had a significant relationship (p=0.022), but the expression of the p53 protein and the ER had no significant correlation. In conclusion, these results suggest that the expression of the p53 protein and the PR may play a role in development and growth of soft tissue leiomyosarcoma. Further studies of large numbers are needed to clarify the exact relationship between tumorigenesis and the p53 and the PR expressions in leiomyosarcoma of soft tissue.

Estrogen Receptor Analysis in Fine Needle Aspirates and Frozen Sections from Human Breast Carcinomas.: Gyung Yub Gong, Se Hyun Ahn, Kun Choon Park, Ghee Young Choe, Eun Sil Yu, In Chul Lee; Korean J Cytopathol. 1994;5(1):10-14.

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Abstract PDF: The expression of sex steroid hormone receptors by neoplastic cells is an important predictor of response to hormone therapy. Thus, the selection of treatment modality is often based on the identification of receptors in tumor tissue. Various monoclonal antibodies of high specificity are now available for analyzing the estrogen receptor(ER). With these antibodies, biochemical enzyme immunoassay and immunohistochemistry using histologic sections have been used for ER analysis. We used fine needle aspirates from 15 human primary breast carinomas for the analysis of ERs. The semiquantitative receptor values obtained in cytologic specimens were correlated well with those from histologic specimens. The results of ER in fine needle aspirates were concordant with ER in histologic specimens(r=0.94). Only three cases showed a little difference in staining intensity and proportion of positive cells. Our results showed a good correlation between the receptor values determined in cytologic smears and those determined in tissue sections. It is suggested that measurement of the ER in cytologic smears may be a reliable technique which can be performed on aspiration cytologic samples.

S Phase Kinase Associated Protein 2 Expression in Breast Cancer and Its Prognostic Implications.: Eun Deok Chang, Eun Jung Lee, Se Jeong Oh, Chang Suk Kang; Korean J Pathol. 2005;39(2):69-73.

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Abstract PDF: BACKGROUND
S Phase Kinase Associated Protein 2 (Skp2), an F-box protein necessary for DNA replication, has recently been demonstrated to be an oncogene. The purpose of this study was to examine the Skp2 expression and to investigate its association with expressions of estrogen receptor (ER), androgen receptor (AR) and HER-2, as well as clinicopathological variables including tumor recurrence.
METHODS
The expressions of Skp2, ER and AR were examined by immunohistochemistry and HER-2 amplification by chromogenic in situ hybridization (CISH) in 117 cases of breast carcinoma.
RESULTS
Skp2 was expressed in 26 patients (22.2%) and was significantly correlated with tumor type (p=0.031), tumor grade (p=0.017) and ER expression (p=0.038). Twenty four (20.5%) of 117 patients had a tumor recurrence, and 6 patients (5.1%) died of multifocal metastases. Tumor recurrence was significantly correlated with histological grade (p=0.041) and lymph node status (p<0.001).
CONCLUSIONS
Although Skp2 expression was statistically insignificant in association with tumor recurrence, it might be useful as a biologic predictor in breast cancer. The simple and reliable immunohistochemical assay presented in this study can be a routine part of breast cancer evaluation and may influence patient management.

The Difference of Cathepsin D Expression between Invasive Ductal Carcinoma and Ductal Carcinoma In Situ of the Breast.: Hye Kyoung Yoon, Soo Jin Jung; Korean J Pathol. 2004;38(6):408-414.

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Abstract PDF: BACKGROUND
It is known that cathepsin D expression in host stromal cells is associated with a more aggressive tumor behavior in breast cancers.
METHODS
Cathepsin D expression was examined in 222 cases of invasive ductal carcinoma (CA) and 25 cases of ductal carcinoma in situ (DCIS) by the immunohistochemical staining. Cathepsin D expression was evaluated according to the expression site, either in the tumor cells (CD-T) or in the stromal cells (CD-S), and graded according to the immunopositivity. The differences of CD-T and CD-S in each case were evaluated according to the pathologic parameters and estrogen receptor (ER)/progesterone receptor (PR) status.
RESULTS
The rate of CD-S was significantly higher in the CA than in the DCIS (p<0.0001). In the CA, the rate of CD-S was higher than that of CD-T, while in the DCIS, the rate of CD-T was higher than that of CD-S. In the CA, the rate of CD-S and the tumor grade showed a positive relationship (p=0.0281). There were positive correlations between the ER positivity and CD-S (p=0.0236), and between the PR positivity and CD-T (p=0.0246). For the DCIS, no significant relationships were noted between the pathologic parameters including ER/PR status and CD-T/CD-S.
CONCLUSION
Cathepsin D expression in the stromal cells seems to be related to the invasiveness and aggressive biological behavior in breast cancers. In addition, there might be some relationship betweeen the ER positivity and CD-S, and between the PR positivity and CD-T.

Immunohistochemical Study of Heat Shock Protein(HSP) and Estrogen Receptor(ER) in the Normal Endometrium and in Adenocarcinoma of the Endometrium.: Hyuni Cho, Aeree Kim, Yung Suk Lee, Han Kyeom Kim, Insun Kim; Korean J Pathol. 1995;29(2):205-211.

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Abstract PDF: Heat shock protein(HSP), first found in the MCF-7 human breast tumor cell line is one of the estrogen-regulated proteins and its synthesis is stimulated by estradiol. In this study, immunohistochemical staining was done for estrogen receptor(ER) and HSP on formalin-fixed, paraffin-embedded tissue sections in twelve normal cyclic and twenty carcinomatous endometria. 1) During the proliferative and early secretary phases, the nuclei of surface and glandular epithelial cells and stromal cells had moderate to strong staining for ER, whereas during the mid and late secretary phases, the glandular epithelial and stromal cells had weak staining for ER. The surface epithelial cells had positive staining of variable intensity. 2) From the early proliferative to mid secretary phases, the glandular and surface epithelial cells showed a positive reaction of variable intensity for HSP. In the late secretary phase, the glandular and surface epithelial cells showed a weak positive or a negative reaction for HSP. During the menstrual cycle, the stromal cells remained negative for HSP. 3) In adenocarcinomas of the endometrium, 8 of 11 (72.7%) well differentiated carcinomas were positive for both ER and HSP, while only 3 of 9(33.3%) moderately and poorly differentiated carcinomas were positive for ER and HSP. In conclusion, ER and estrogen-regulated heat shock protein(HSP) were closely related in normal and carcinomatous endometria and the reactivity was decreased according to poor differentiation.

Relationship between Immunohistochemical Expression of Cathepsin D and Other Prognostic Factors of Breast Carcinoma.: Kwang Hwa Park, Byeng Woo Park, Kyong Sik Lee, Kwang Gil Lee; Korean J Pathol. 1994;28(6):612-619.

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Abstract PDF: The cathepsin D is a lysosomal protease secreted in excess by breast cancer cells. The function of this enzyme is degradation of the extracellular matrix and proteoglycan. It is induced by estrogens in estrogen receptor positive breast cancer cell lines. On the basis of this, cathepsin D expression in breast cancer cells seems to be correlated with the prognosis. But there is debates in its prognostic significance. Relationship between cathepsin D expression and other prognostic factors of breast cancer was studied. We investigated 51 cases of invasive ductal cell carcinoma of breast removed by open biopsy or mastectomy. All cases were fixed in formalin and embedded in paraffin. We used 46-KD intermediate form of the enzyme for cathepsin D expression on immunohistochemical stain. We observed no significant correlation with age, stage, histologic grade, lymphatic invasion, and estrogen receptor status. Cathepsin D may be an independent factor which is not related with other prognostic factors, especially estrogen receptor status.

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