Estrogen receptors in human nontarget tissues: biological and clinical implications.
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Animals↗
Biomedical subjects
D R Ciocca
Publications and source records attributed to D R Ciocca.
Growth hormone-releasing hormone in testicular interstitial and germ cells: potential paracrine modulation of follicle-stimulating hormone action on Sertoli cell function.
GH-releasing hormone (GHRH) is present in the interstitial and germ cells of the rat testis. In previous studies we found that GHRH is secreted from rat adult Leydig cells, in which it stimulates basal and LH-induced cAMP formation and steroidogenesis. In other studies cAMP production in Sertoli cells was found to be stimulated by GHRH. In the present report, we describe a potential paracrine action of GHRH in the Sertoli cell, with stimulation of cAMP formation in cultured adult and pubertal Sertoli cells. GHRH increased FSH-stimulated cAMP production in adult and pubertal cultures in a time-dependent manner. GHRH stimulation of basal and FSH-induced extracellular cAMP formation was more prominent in pubertal than in adult cultures. Immunocytochemical studies demonstrated the presence of GHRH-like immunoreactivity in rat interstitial cells from day 4 to adult life and in the acrosomal region of early and intermediate spermatids at stages III-VI of the seminiferous epithelium cycle. Immunoreactive GHRH was not observed in late spermatids and mature sperm or in Sertoli cells at any age. These results indicate that GHRH acts synergistically with FSH to promote cAMP production in Sertoli cells in culture. Testicular GHRH of Leydig and germ cell origin may be an important paracrine regulator of Sertoli cell function. Alternatively, GHRH present in germ cells may exert stage-specific intracrine functions.
Aging↗
Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review.
Heat shock and other environmental and pathophysiologic stresses stimulate synthesis of heat shock proteins (Hsps). These proteins enable the cell to survive and recover from stressful conditions by as yet uncompletely understood mechanisms. Hsp27 is an important small Hsp (molecular weight, 27,000) found in human cells--both cancer cells and normal cells. This protein, besides its putative role in thermotolerance, is of special clinical interest because of recent data suggesting it may also play a role in drug resistance. In adults, Hsp27 is found particularly in several cell types such as breast, uterus, cervix, placenta, skin, and platelets. Although low-molecular-weight (small) Hsps have been found to be involved in embryogenesis of Xenopus and Drosophila, they have not been detected in human fetal organs. Regulation of expression of the Hsp gene (also known as HSPB1) has been considered a paradigm of gene regulation and is actively being studied in both prokaryotes and eukaryotes. In prokaryotes, the major Hsp genes are transcriptionally regulated by positively and negatively acting transcription factors. In eukaryotes, the genes encoding Hsps contain a regulatory DNA motif (inverted repeats of the pentameric sequence nGAAn) known as the heat shock element. Hsp27 may function as a molecular chaperone and in signal transduction pathways of different cell regulators, and Hsp27 and other Hsps may be active in development of resistance to stressful conditions and agents including cytotoxic drugs. Study findings indicate that some but not all estrogen-positive breast cancers express Hsp27, and overexpression of Hsp27 has been associated with both good and poor prognosis. In endometrial carcinomas, the presence of Hsp27 is correlated with the degree of tumor differentiation as well as with the presence of estrogen and progesterone receptors. Studies suggest, however, that detection of Hsp27 should not be considered to be a method for identifying hormone-responsive tumors or detecting estrogen receptors. Hsp27 seems to be a biochemical marker of estrogenic endometrial response. In patients with cervical cancer, Hsp27 is predominantly expressed in well-differentiated and moderately differentiated squamous cell carcinomas. In addition, expression of Hsp27 seems to be a negative prognostic factor for gastric cancer. Different isoforms of Hsp27 have been found in lymphoid tissue of patients with acute lymphoblastic leukemia, and the protein has also been associated with viral infections. These aspects are summarized and discussed in the present review.
Animals↗
Estrogen receptor, progesterone receptor, and HER-2/neu protein in breast cancers from pregnant patients.
BACKGROUND: Because the occurrence of breast cancer during pregnancy is uncommon and because the high levels of estrogens and progestins associated with pregnancy could cause false-negative results from ligand binding assays (LBA), the actual incidence of steroid hormone receptor positivity in tumors from this subset of women is unclear. METHODS: Estrogen receptor (ER) and progesterone receptor (PgR) were determined using LBA methods in 15 tumors from 15 pregnant patients with breast cancer. In addition, immunohistochemistry was done for ER, PgR, pS2, heat shock protein 27 (hsp27), and HER-2/neu on 12 of the 15 tumors. RESULTS: Five of 15 (33%) tumors were positive for ER by LBA, compared with 52% of tumors from age-matched nonpregnant patients. Six of 12 (50%) were ER-positive by immunohistochemistry. For PgR, 7 of 15 (47%) tumors were positive by LBA, compared with 42% of tumors from nonpregnant patients. Ten of 12 (83%) stained positive for PgR. By LBA, 67% of tumors studied were positive for ER or PgR or both, as opposed to 57% of tumors from the nonpregnant comparison group. Two other estrogen receptor-mediated proteins, pS2 and hsp27, were present by staining in 8 of 12 (67%) and 10 of 12 (83%) of tumors, respectively. Seven of 12 tumors (58%) had positive staining for HER-2/neu, whereas only 16% of age-matched nonpregnant patients had positive-staining tumors. CONCLUSION: By LBA, the incidence of ER and PgR in breast tumors from pregnant women was not significantly different from that of tumors from nonpregnant age-matched patients. Some ER-negative tumors were PgR, pS2, or hsp27 positive, indicating that an intact estrogen response system was operative although ER was not detectable by standard LBA.
Adult↗
Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications.
BACKGROUND: Cell synthesis of heat shock (stress-response) proteins is increased by a variety of environmental and pathophysiological stressful conditions. The 70-kd heat shock protein (hsp70) is thought to be involved in protein-protein interactions including those of the protein products of the human c-myc oncogene and the p53 (also known as TP53) tumor suppressor gene. PURPOSE: The purpose of this study was to investigate whether elevated hsp70 expression may be an indicator of biological stress experienced by a breast cancer and may, therefore, predict disease outcome. METHODS: Levels of hsp70 were determined by Western blot analysis in primary breast tumors from patients with negative axillary lymph nodes. We performed exploratory data analyses on a set of 162 primary breast cancers and constructed prognostic indexes of hsp70 expression levels. The optimal cutpoint for hsp70 expression was considered to be the value yielding the greatest separation for disease-free survival for the resulting two groups of patients. That cutpoint was then validated in a set of 345 tumors by univariate and multivariate analyses. Data were analyzed for overall survival, disease-free survival, tumor size, and patient age, as well as estrogen receptor and progesterone receptor status, ploidy (DNA content), and percentage of cells in S phase as determined by flow cytometry. RESULTS: Expression of hsp70 emerged as a useful prognostic factor, both in univariate and in multivariate analyses. Patients whose tumors had high expression of hsp70 had significantly shorter disease-free survival (P = .006). The other statistically significant factors were S-phase fraction (P = .008) and tumor size (P = .01). For patients who received adjuvant therapy, hsp70 was the only independent predictor of disease recurrence (P = .05). For those with tumors 1-3 cm in diameter, hsp70 (P = .008) and S-phase fraction (P = .02) were statistically significant predictors of recurrence. CONCLUSIONS: Measurement of hsp70 expression in primary tumors from patients with node-negative breast cancer may be useful in identifying patients at high risk for disease recurrence and thus may affect decisions regarding treatment after surgery. IMPLICATIONS: Future studies should be performed to determine if detection of hsp70 by immunohistochemistry can be used to predict clinical outcome and to better understand the relationships between hsp70 and the effects of various treatment modalities.
Analysis of Variance↗
Measurement of steroid hormone receptors in breast cancer patients on tamoxifen.
Estrogen (ER) and progesterone receptor (PgR) positive breast tumors often respond to tamoxifen, but ultimately progress as they become tamoxifen resistant. An accurate assessment of receptor status in specimens from tamoxifen-resistant patients could help to understand potential mechanisms of resistance and to predict response to second line hormonal therapies. However, since tamoxifen itself can affect ER and PgR determinations, assay results can be misleading. We measured ER and PgR by both ligand binding (LBA) and immunohistochemical (IHC) assays in 34 tumors from patients on tamoxifen, 30 of whom were displaying resistance to the drug. These tumors were classified into several receptor phenotypes. Eleven patients, 8 of whom were clearly progressing, expressed both receptors while on tamoxifen. ER was significantly less often negative when measured by IHC, suggesting that ER status by LBA was falsely negative in this group due to receptor occupancy by tamoxifen. Six patients had no detectable ER by LBA or IHC but still expressed PgR. The presence of PgR suggests that ER could still be functional, though undetectable, in these tumors, or that PgR is constitutively expressed by them. Finally, 12 patients were ER and PgR-negative by both assays, suggesting hormonal independence as the mechanism for resistance in this group. In a subset of patients with receptor assays both prior to tamoxifen and at the time of progression while taking the drug, we found that most ER-positive tumors converted to an apparent ER-negative status when assayed by LBA, while PgR status frequently remained unchanged. The continued expression of ER and/or PgR in many patients with tumor progression on tamoxifen indicates that mechanisms for resistance other than receptor loss are common in breast cancer.
Adult↗
Serotonin secretion from rat Leydig cells.
In rat Leydig cells, serotonin (5HT) binds to 5HT2 receptors and stimulates the secretion of CRF which in turn acts as an inhibitor of gonadotropin-induced cAMP formation and androgen production. In the present study we defined the regulation of 5HT secretion in cultured Leydig cells. Adult Leydig cells secreted considerable quantities of 5HT (100-150 pg/10(6) cells per 10 min). The release of 5HT was acutely stimulated by hCG (ED50, 1.1 pM) with maximal stimulation at 10 pM hCG (160%). Forskolin also increased (+220%) 5HT release from cultures (ED50, 50 nM) while TPA was much less effective (+20%), indicating a major role for cAMP in gonadotropin-induced 5HT release. This was confirmed by the finding that 8-Br cAMP (1 mM) was an effective stimulus of 5HT release (+360%). Similar increases of 5HT release by hCG were observed in the absence of extracellular Ca2+. However, ionomycin was a potent stimulus of 5HT release, indicating that elevation of cytoplasmic [Ca2+] could also induce amine secretion. The 5HT content of Leydig cells ranged from 300 to 350 pg/10(6) cells, and decreased during stimulation of 5HT release. Also, immunohistochemical studies revealed specific staining of 5 HT in interstitial cells of the adult rat testis. These studies demonstrated that rat Leydig cells contain and secrete 5HT, and that 5HT release is stimulated by gonadotropin acting primarily through a cAMP-mediated mechanism.
8-Bromo Cyclic Adenosine Monophosphate↗
Steroid receptors and heat-shock proteins in patients with primary biliary cirrhosis.
Primary biliary cirrhosis has a definite female preponderance. Increased estrogen levels have been found in patients with this disease; however no studies indicate the status of sex hormone steroid receptors in primary biliary cirrhosis patients. In this study the occurrence and distribution of estrogen receptors, progesterone receptors and androgen receptors in liver biopsy specimens from patients with primary biliary cirrhosis were examined and compared with these receptors in the normal liver. In addition, three heat-shock proteins associated with steroid receptors (90 kD, 70 kD and 27 kD) were examined. All of the receptor proteins were detected on immunocytochemical study using specific receptor antibodies; monoclonal and polyclonal antibodies were also used to detect the heat-shock proteins. Normal bile duct epithelial cells displayed low-to-moderate amount of estrogen receptors and abundant 90- kD, 70- kD and 27-kD heat-shock protein expression, whereas normal hepatocytes showed moderate estrogen receptor and 90-kD heat-shock protein and high 70-kD heat-shock protein expression. Expression of 70-kD heat-shock protein was due mainly to the constitutive form of this protein (hsc72). In patients with primary biliary cirrhosis, significant increases in estrogen receptor and 90-kD heat-shock protein content were seen in bile duct cells and in hepatocytes. Levels of 27-kD heat-shock protein were also increased in some of the primary biliary cirrhosis biopsy specimens. The expression of progesterone receptor and androgen receptor was very low in normal and primary biliary cirrhosis bile duct cells and hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Correlation of HER-2/neu amplification with expression and with other prognostic factors in 1103 breast cancers.
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Breast Neoplasms↗
Response of human breast cancer cells to heat shock and chemotherapeutic drugs.
Previous studies have shown that certain chemotherapeutic drugs are less effective on tumor cells when cells have been previously exposed to hyperthermia. In the present study, we have evaluated whether specific modifications in heat shock protein (hsp) expression are associated with resistance to anticancer drugs. RNA levels for hsp90, hsp70, and hsp27 were studied by Northern and slot blots, while proteins were studied by two-dimensional gel electrophoresis, in MCF-7/BK and MDA-MB-231 breast cancer cells. The sensitivities of these cells to doxorubicin, colchicine, 5-fluorouracil, cisplatin, actinomycin D, and methotrexate were tested by clonogenic assays. These techniques were applied to both cell lines before (control) and after heat shock. The study revealed that elevated hsp70 and hsp27 levels were associated with doxorubicin resistance. In addition, the presence of phosphorylated hsp27 isoforms was also associated with doxorubicin resistance. The study showed that elevated hsps were not associated with multidrug resistance. Heat shock did not induce P170 glycoprotein mRNA overexpression or resistance to the other drugs tested. We also found that the level of doxorubicin protection conferred by the overexpression of hsp was lower than that obtained in cells expressing a multidrug resistance phenotype (MDA-A1R cells). In these cells, heat shock did not confer additional doxorubicin resistance and hsp27 phosphorylation was deficient. Our studies suggest that specific hsps are associated with doxorubicin resistance in certain human breast cancer cells and that this mechanism seems to be independent of the multidrug resistance system.
Breast Neoplasms↗
Effect of human papillomavirus infection on estrogen receptor and heat shock protein hsp27 phenotype in human cervix and vagina.
In this study we have explored whether, as a consequence of human papillomavirus (HPV) infection, there is inappropriate expression of estrogen receptor and/or of a small heat shock protein of 27,000 daltons (hsp27). Estrogen receptor, hsp27, and HPV structural antigens were detected by immunocytochemistry, while HPV DNA (6/11, 16/18, 31/35/51) was determined by in situ hybridization in cervical and vaginal samples from 40 patients. Most of the samples with HPV infection without atypia showed a shift in estrogen receptor expression since this protein appeared mainly in the intermediate and superficial cell layers. In the serial sections, these layers displayed strong estrogen receptor staining, together with high HPV replication and late HPV gene expression. In the samples with HPV infection and atypia, estrogen receptors were also frequently found in the basal and parabasal cells, but almost 20% of these samples did not show estrogen receptors. The presence of high estrogen receptor expression was not dependent on a particular HPV DNA type. On the other hand, interesting modifications in hsp27 expression were observed in the HPV-infected tissues. The cytoplasm of the cells with koilocytotic changes showed very low hsp27 content. In several samples this protein appeared in the nuclei of the superficial cells, and sometimes it was also observed in the cytoplasm of the basal cells. These changes in estrogen receptor and hsp27 expression suggest that these proteins might have a role in virus-host biology.
Antigens, Viral↗
Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients.
PURPOSE: The antiestrogen tamoxifen is effective in therapy for breast cancer. However, its use is limited by the eventual development of acquired tamoxifen resistance in many patients. The mechanisms responsible for tamoxifen resistance remain unknown; loss of estrogen receptor (ER), selection of hormone-independent breast cancer clones, or alterations in serum tamoxifen levels after long-term use do not explain acquired resistance in most patients. Using an experimental model in which human breast cancer cells develop resistance in athymic mice treated with tamoxifen, we have recently shown that acquired resistance is associated with markedly reduced cellular concentrations of tamoxifen and by isomerization of the trans-4-hydroxy metabolite to the less potent cis isomer. MATERIALS AND METHODS: Using a sensitive high-performance liquid chromatography (HPLC) assay, we have now measured levels of tamoxifen and its major metabolites in a series of 14 tumors from patients treated with tamoxifen. The duration of therapy ranged from 1 month to 6 years. RESULTS: Tumor tamoxifen levels varied over a wide range. Low concentrations were observed in tumors from eight patients, all demonstrating progressive disease at the time of biopsy after a minimum duration of treatment of 6 months. Six tumors had moderate to high tamoxifen levels, two from patients responding to tamoxifen, one from a patient with stable disease, and three from patients with disease progression. Both the cis and trans isomers of the potent antiestrogenic metabolite 4-hydroxy-tamoxifen were detected in 11 tumors. Six tumors had high ratios of the cis to trans isomer (1.10:2.06), all from patients not responding to tamoxifen. The five tumors with low cis:trans ratios included the two tumors from responding patients and three from patients with progression. All but one of the 11 nonresponding patients had either a low tumor tamoxifen level, a high cis:trans ratio, or both. CONCLUSION: This study clearly demonstrates a wide range of tumor tamoxifen levels and accumulation of the less antiestrogenic cis isomer of 4-hydroxytamoxifen in some patients on tamoxifen therapy. Additional study is necessary to determine if these metabolic profiles are related to the development of tamoxifen resistance.
Adult↗
Immunological evidence for the identity between the hsp27 estrogen-regulated heat shock protein and the p29 estrogen receptor-associated protein in breast and endometrial cancer.
Previous studies have shown several similarities between an estrogen-regulated heat shock protein of 24,000-28,000 daltons (hsp27), and a cytoplasmic estrogen receptor-associated protein of 27,000-29,000 daltons (p29). These proteins have been studied by monoclonal antibodies generated in different laboratories. In the present report we have performed immunocytochemical and immunoblot studies to explore if the monoclonal antibodies against hsp27 (C11) and against p29 (ER-D5) may be identifying the same protein. Breast and endometrial carcinomas and normal endometrial samples were examined by immunocytochemistry (in mirror sections and by double-immunostaining). Identical hsp27 and p29 immunostaining intensity, distribution, and percentage of stained cells was demonstrated by immunocytochemistry. The antigens examined by the two antibodies appeared in the same cells. Cytosols from tumors analyzed by the Western blot technique revealed that the C11 and the ER-D5 antibodies recognized bands with identical electrophoretic mobility. Immunoprecipitation studies with one antibody, C11, followed by Western blot showed that the precipitate was reactive with both antibodies. Identical C11 and ER-D5 reacting spots were observed after blotting proteins separated by high resolution two-dimensional gel electrophoresis. In addition, p29 protein was induced by heat shock in the estrogen receptor negative MDA-MB-231 human breast tumor cell line. These results strongly suggest that the two proteins under investigation are identical.
Antibodies, Monoclonal↗
Estrogen receptors, progesterone receptors and heat-shock 27-kD protein in liver biopsy specimens from patients with hepatitis B virus infection.
It has been proposed that in the human liver, the estrogen receptor gene may become inappropriately expressed as a consequence of HBV integration, contributing to cell transformation. This study was undertaken to examine estrogen receptor status in patients with hepatitis B virus infection and to analyze the expression of progesterone receptor and of a heat-shock 27,000-D protein (hsp27), both of which are estrogen regulated in estrogen target tissues. Receptor proteins were detected in liver biopsy specimens by immunocytochemistry using antireceptor monoclonal antibodies; a monoclonal antibody was also used to detect hsp27. Estrogen receptor and progesterone receptor were mainly seen in the nuclei of hepatocytes. The presence of hepatitis B virus infection did not always result in elevated estrogen receptor expression, but in general the expression of this receptor protein was higher in hepatitis B virus-positive patients than in patients with the same pathological findings (hepatitis, cirrhosis, hepatocarcinoma) but without hepatitis B virus. This was more clearly seen in the patients with hepatitis. Although estrogen receptor expression was moderate to high in many samples, the expression of the two biochemical markers of estrogen action at postreceptor levels (progesterone receptor and hsp27) was low or absent in most of the liver tissues examined, suggesting that in the liver the interaction of estrogen-estrogen receptor-DNA has characteristics inherent to this tissue.
Adolescent↗
Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue.
We have studied by immunocytochemistry and monoclonal antibodies the presence and localization of estrogen receptors, progesterone receptors, and a 24-kD estrogen-regulated heat shock protein in biopsies from breast and endometrial cancer patients. Three different tissue processing protocols were used to colocalize the antigens in the same tissue sections: a) frozen sections, b) formalin fixation with routine paraffin embedding, and c) picric acid-formaldehyde (PAF) fixation with a rapid embedding in paraffin. Frozen sections showed good receptor staining but poor 24-kD protein immunoreactivity, while routine paraffin sections (with or without DNase pretreatment) were inadequate to reveal the nuclear receptor proteins at the same level seen in frozen sections. On the other hand, all three proteins could be detected satisfactorily in PAF-fixed paraffin-embedded tissue. Using this procedure we were able to visualize 24-kD protein and estrogen receptor or progesterone receptor in individual cells in paraffin sections. The study revealed that in all of the estrogen receptor positive breast and endometrial tumor samples, almost 90% of the cells expressing the cytoplasmic 24-kD protein contained estrogen receptor in the cell nucleus. In contrast, 24-kD immunoreactive cells did not express progesterone receptors in almost 40% of the progesterone receptor positive tumor samples.
Adenocarcinoma↗
Corticotropin-releasing hormone, luteinizing hormone-releasing hormone, growth hormone-releasing hormone, and somatostatin-like immunoreactivities in biopsies from breast cancer patients.
The presence of immunoreactive adrenocorticotropin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LHRH), growth hormone-releasing hormone (GHRH), and somatostatin has been investigated by immunohistochemistry in forty biopsies from breast cancer patients. All of these hypothalamic hormones were found in about 30% of the samples, seen in the cytoplasm or in the nuclei of the tumor cells. Positive immunostaining for the hypothalamic hormones was present in colloid, lobular, and infiltrating ductal carcinomas. There was not a clear relationship between occurrence of staining for the hypothalamic hormones and the histologic grade of tumors or the clinical stage of the disease. Immunoreactive LHRH was more frequently found in breast tumors with estrogen and progesterone receptors. On the other hand, preneoplastic breast lesions expressed mainly somatostatin, while immunoreactivity was absent in normal mammary tissue.
Biopsy↗
Analysis of a 24-kilodalton (KD) protein in the human uterine cervix during abnormal growth.
The authors have previously studied the presence and distribution of a 24-kilodalton (KD) estrogen-regulated protein in the human normal cervix (Am J Obstet Gynecol 1986; 155:1090-1096). This protein has recently been identified as a heat-shock protein, and in order to continue its study the authors have now examined its expression in preneoplastic to neoplastic cervical samples. The study involved 53 patients, the presence of 24-KD protein together with keratin and carcinoembryonic antigen (CEA) was investigated by immunohistochemical analysis. Cytosol samples from 15 patients with squamous cervical carcinomas were also studied by the Western blot technique, and the presence of estrogen receptors was analyzed biochemically. The 24-KD protein was observed in cervical intraepithelial neoplasias (CIN), but it was not useful to identify the different degrees of CIN examined. The 24-KD protein, keratin, and CEA were predominantly expressed in well and moderately differentiated squamous carcinomas in the more differentiated areas, and the protein was also found in cervical adenocarcinomas. The presence of 24-KD protein did not correlate with that of estrogen receptors in squamous cervical carcinomas. The Western blot and the immunohistochemical studies revealed that the antibody to 24-KD protein does not cross-react with epitopes of CEA and keratins.
Adenocarcinoma↗
Study of estrogen receptor, progesterone receptor, and the estrogen-regulated Mr 24,000 protein in patients with carcinomas of the endometrium and cervix.
The presence of an estrogen-regulated protein with 24,000 molecular weight has been studied in 47 patients with endometrial carcinomas and in 29 patients with cervical carcinomas in order to correlate its presence with that of estrogen receptors (ERs) and progesterone receptors (PgRs). In the cytosol tumor samples the Mr 24,000 protein was detected by the Western blot technique using a monoclonal antibody (C11), while the presence of ER and PgR was studied by the one-point dextran-coated charcoal assay. In the tumor tissue sections immunohistochemistry was applied to detect Mr 24,000 protein, ER, and PgR; in these cases monoclonal antireceptor antibodies (H222 and mPRI) were used to localize the receptor proteins. In endometrial and endocervical adenocarcinomas the presence of Mr 24,000 protein correlated significantly with that of ER (P less than or equal to 0.05) in the cytosol samples; when the evaluation was performed in the tumor sections, the presence of Mr 24,000 protein correlated with that of ER (P less than or equal to 0.005) and PgR (P less than or equal to 0.05) as well. The study also showed that almost 70% of the well-differentiated adenocarcinomas had ER, PgR, and Mr 24,000 protein. In 25% of the endometrial adenocarcinomas examined the tumors were associated with normal, proliferative, and hyperplastic endometrium; in these cases the presence of ER, PgR, and Mr 24,000 protein was evaluated by immunohistochemistry in the malignant and nonmalignant endometrium. On the other hand, there was a lack of correlation between Mr 24,000 protein, ER, and PgR in the squamous carcinomas of the uterine cervix and in the endometrial adenocarcinomas with squamous cells. In most of these cases the tumors lacked ER and PgR although 80% of them contained the Mr 24,000 protein to a variable degree. It is suggested that Mr 24,000 protein is involved in growth and differentiation (the Mr 24,000 protein is a heat shock protein) and that the gene coding of this protein is under hormonal control only in those tissues where growth and differentiation are strongly hormonally controlled (breast and endometrium).
Adenocarcinoma↗