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At least 19 recordsLinked to original sources
PubMed2002

The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2.

PURPOSE: The morphologic and molecular phenotype of breast cancers may help identify patients who are likely to carry germline mutations in BRCA1 and BRCA2. This study evaluates the immunohistochemical profiles of tumors arising in patients with mutations in these genes. MATERIALS AND METHODS: Samples of breast cancers obtained from the International Breast Cancer Linkage Consortium were characterized morphologically and immunohistochemically using antibodies to estrogen receptor, progesterone receptor, HER-2 (c-erbB-2 oncogene), and p53 protein. RESULTS: Breast cancers in patients with BRCA1 germline mutations are more often negative for estrogen receptor, progesterone receptor, and HER-2, and are more likely to be positive for p53 protein compared with controls. In contrast, BRCA2 tumors do not show a significant difference in the expression of any of these proteins compared with controls. CONCLUSION: BRCA1 has a distinctive morphology and immunohistochemical phenotype. The combined morphologic and immunohistochemical data can be used to predict the risk of a young patient harboring a germline mutation in BRCA1. The BRCA2 phenotype is currently not well defined.

Adult↗
PubMed1984

Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer.

The relationships between estrogen receptor, progesterone receptor, and a variety of patient characteristics are described for 2,977 women with primary breast cancer. Older women were more likely to be estrogen-receptor positive than younger women. When patient age and menopausal status were analyzed together, age was found to be the primary determinant of increased estrogen-receptor concentrations. There appeared to be no relationship with progesterone receptor for either age or menopausal status when these variables were analyzed separately. But premenopausal women had higher progesterone receptor concentrations than postmenopausal women when patients of the same age were compared, perhaps reflecting greater estrogen-mediated synthesis of progesterone receptor. Tumor size was negatively related to steroid receptor concentrations, but no relationships were observed between steroid receptors and either the number of positive axillary lymph nodes or the location of the primary tumor.

Adult↗
PubMed2006

A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically in premenopausal women.

OBJECTIVE: To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically. STUDY DESIGN: Thirty-two premenopausal women affected by uterine leiomyomas were randomized into two equal groups. Group A was treated with gosereline (3.6 mg subcutaneous injection monthly) and group B was treated with raloxifene (60 mg daily per os) for 3 months before undergoing surgery. At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and p53 were calculated. The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared between groups. RESULTS: The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm(3) to 35 cm(3), and in raloxifene group from 68 cm(3) to 50 cm(3), p<0.05. The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant. H-score of ER expression was significantly lower in gosereline group compared to control group (54.4 versus 113.2, p = 0.001), whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene versus 94.7 for control, p = 0.001). The p53 expression was only lower with gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there was no significant change between the raloxifene group and the control group (201.9 versus 205.6) (p>0.05). CONCLUSION: Raloxifene was as effective as gosereline in reducing leiomyoma volumes. Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment. In both treatment modalities, the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies.

Adult↗
PubMed1998

Regulation of oxytocin receptor in the placentome capsule throughout pregnancy in the ewe: the possible role of oestradiol receptor, progesterone receptor and aromatase.

UNLABELLED: The hormonal regulation of uterine oxytocin receptors (OTR) during the establishment of pregnancy and at parturition has been studied extensively, but little information is available during mid-pregnancy. This study investigated the localisation of OTR mRNA in the ovine placentome throughout gestation and related this to expression patterns for the putative regulatory agents aromatase, oestradiol receptor, progesterone receptor and oxytocin. Placentomes were collected at regular intervals throughout pregnancy for in situ hybridisation analysis and immunocytochemistry (oestradiol receptor only). Results were quantified by optical density measurements of autoradiographs. Progesterone receptor mRNA was localised to the caruncular tissues on day 30 but became undetectable by day 34. Aromatase mRNA appeared in the fetal villi at days 34-40, with concentrations peaking at days 52-55 and again at days 132-137. Oestradiol receptor mRNA was localised to the caruncular tissues from days 13 to 30 and found in the maternal villi and placentome capsule from days 45 to 70. Oestradiol receptor protein was barely detectable in either tissue. OTR mRNA was localised to the placentome capsule at days 34-40, remaining high at day 45 and declining to basal levels by days 132-137. Oxytocin mRNA was not detected in the placentome. IN CONCLUSION: (1) progesterone acting via its receptor may suppress the expression of aromatase and OTR in early pregnancy; (2) the up-regulation of OTR expression in the capsule may not involve the oestradiol receptor; (3) there is a differential regulation between different regions of the uterus as the increase in the placentome capsule occurs at a time when concentrations in the rest of the endometrium and myometrium remain low; (4) oestradiol receptor expression in the placentome may be regulated at the translational level; and (5) there is no local production of oxytocin in the sheep placenta. The role of ORTs in the capsule during mid-pregnancy remains to be determined.

Animals↗
PubMed1990

[Effect of decapeptyl (D-TrpG GnPh) on estrogen receptors, progesterone receptors and tissue levels of estrogens (non-conjugated and sulfate-conjugated) in patients with uterine myoma].

Concentrations of estrogen receptors, progesterone receptors, unconjugated estrogens (estradiol and estrone) and sulfate-conjugated estrogens (estradiol sulfate and estrone sulfate) were determined in patients treated with Decapeptyl and in controls. After prolonged Decapeptyl therapy, a highly significant fall in progesterone receptors was evidenced; estrogen receptors were found to be decreased in the myoma as compared with the secretory phase in controls and in the myometrium as compared with the proliferative phase in controls. Tissue levels of estrone sulfate and estradiol sulfate decreased very substantially. In conclusion, Decapeptyl emerges as a very promising agent for the treatment of uterine myomas.

Antineoplastic Agents↗
PubMedDate not supplied

The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen.

OBJECTIVE: To enlighten the early response of endometrium to tamoxifen by assessing the expression of estrogen receptors, progesterone receptors, Ki-67, and the histological response in endometria from normal postmenopausal women treated for 21 days with tamoxifen. DESIGN: A total of 40 women, scheduled to undergo vaginal hysterectomy because of uterine prolapse, were randomly assigned to the tamoxifen group (20 mg/day; 20 women) or the control group (20 women). Samples were obtained from the upper and the lower thirds of the uterine cavity. Standard immunohistochemical staining of estrogen and progesterone receptors and of Ki-67 was performed on frozen sections. Staining was assessed using semiquantitative immunoreactivity scores. RESULTS: Simple endometrial hyperplasia was diagnosed in 18 of the 20 samples exposed to tamoxifen compared with only 2 of the 20 controls ( P< 0.0005). Staining was increased in both the epithelium and stroma in the tamoxifen samples, a difference that was significant for estrogen receptors in glandular epithelium (180 +/- 80 v 110 +/- 110; P< 0.05). Also, Ki-67 antigen was expressed more frequently in both glandular epithelium ( P< 0.05) and stroma ( P< 0.05) in the tamoxifen samples. CONCLUSIONS: Tamoxifen rapidly up-regulated the cell proliferation markers, an effect that was associated with enhanced growth as confirmed by increased expression of estrogen receptors and Ki-67, in addition to a high incidence of glandular hyperplasia.

Administration, Oral↗
PubMed1991

Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis.

We have determined the estrogen receptor, progesterone receptor (PR), and 1,25-dihydroxyvitamin D3 receptor content of 136 breast carcinomas by an immunocytochemical method. The presence of the three receptors was not related to clinical features of presentation such as T-stage or to age or menopausal status. However, each of the three receptors has a different relationship to the course of the disease in these patients. The presence of PR was significantly associated with an improved overall survival (chi 2 = 4.61, P = 0.032). Patients whose tumors contained immunocytochemically detectable 1,25-dihydroxyvitamin D3 receptor had a longer disease-free interval than those patients with negative tumors (chi 2 = 4.01, P = 0.045). The presence of estrogen receptor and PR were found to correlate with an increased survival between relapse and death (P = 0.027 and P = 0.09, respectively). The relationships between estrogen receptor and PR and prognosis are more apparent when the degree of cell staining is considered. Combined receptor analysis improves our ability to predict the course of the disease and may therefore facilitate better management of the patients.

Adult↗
PubMed2003

The differential expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67 in endometrial polyps.

OBJECTIVE: To obtain a greater understanding of the pathogenesis of endometrial polyps and to gain insight into which factors play a pivotal role in their growth. DESIGN: Retrospective analysis of archived paraffin-embedded specimens. SETTING: St James's University Hospital. SAMPLE: Thirty secretory phase endometrial samples, 10 secretory phase endometrial polyps, 8 proliferative phase endometrial samples and 10 proliferative phase endometrial polyps. METHODS: Immunohistochemistry was used to characterise the expression of oestrogen and progesterone receptors, Bcl-2 and Ki67 in cycling endometrium and phase-matched endometrial polyps. Patterns of expression were compared between the polyps and the endometrium. MAIN OUTCOME MEASURE: The expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67. RESULTS: Three significant differences were found between the endometrium and the polyps. Polyps taken from the proliferative phase of the cycle displayed significantly elevated expression of Bcl-2 and weak or no expression of progesterone receptors. Secretory phase polyps displayed an elevated expression of oestrogen receptors. CONCLUSION: A localised increase in Bcl-2 expression and consequential decline or cessation of apoptosis is an important mechanism underlying the pathogenesis of endometrial polyps. Elevated Bcl-2 expression results in failure of the polyp tissue from undergoing normal cyclical apoptosis during the late secretory phase. This may mean the polyp is not shed along with the rest of the endometrium during menstruation.

Endometrial Hyperplasia↗
PubMed1994

Cloning and in situ hybridization analysis of estrogen receptor, progesterone receptor, and androgen receptor expression in the brain of whiptail lizards (Cnemidophorus uniparens and C. inornatus).

Gonadal steroid hormones act upon specific areas of the vertebrate brain to affect the reproductive physiology and behavior of the animal. Steroid receptors are members of a superfamily of ligand-dependent transcription factors that mediate the effects of steroid hormones by modulating gene expression in the cells containing the receptors. The neuroanatomical distributions of steroid receptor-containing cells have been described for several species by using steroid autoradiography, immunocytochemistry, and more recently in situ hybridization. We have used the polymerase chain reaction to amplify and clone fragments of the estrogen receptor, progesterone receptor, and androgen receptor of whiptail lizards (genus Cnemidophorus). These clones were used to produce probes for use in in situ hybridization assays and to map the neuroanatomical distribution of all three sex steroid hormone receptors in the forebrains of unisexual (C. uniparens) and sexual (C. inornatus) species of whiptail lizards. The distribution of receptor-expressing cells reported here is in general agreement with previous reports in other species with receptor-containing cells concentrated in septal, amygdaloid, cortical, preoptic, and hypothalamic nuclei.

Animals↗
PubMed1994

Strategies for improving the immunohistochemical staining of various intranuclear prognostic markers in formalin-paraffin sections: androgen receptor, estrogen receptor, progesterone receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen revealed by antigen retrieval techniques.

Different variations of the antigen retrieval technique using different retrieval solutions have been evaluated for their effectiveness in restoring the antigenicity of six intranuclear antigens, each of which is a potentially valuable prognostic indicator in formalin-fixed, paraffin-embedded tissue sections. The results of immunohistochemical staining for estrogen receptor, progesterone receptor, androgen receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen were compared following the different antigen retrieval approaches. The strongest immunostaining signal with the clearest background was obtained by microwave heating of dewaxed paraffin sections for 10 minutes in 0.05 mol/L glycine HCl (pH 3.5) or in citrate buffer solution (pH 6). Urea solution, distilled water, and lead thiocyanate solution yielded improvements with some antigens, but less consistently and less impressively than glycine HCl buffer or citrate buffer. Following antigen retrieval nuclear staining was sharply defined and could be achieved consistently in a variety of tissues after formalin fixation for as long as 7 days. The duration of fixation, however, was an important variable; generally, the longer the fixation time the more vigorous the retrieval procedure required. This study demonstrates the ability to stain a variety of intranuclear antigens, which are not readily demonstrable otherwise, in formalin-paraffin sections with a high degree of consistency and reproducibility. The availability of methods that are effective in paraffin sections may facilitate studies of the possible value of these markers as prognostic indicators for predicting the response of major tumors to different forms of therapy. This study also provided insight into the basic principles of the antigen retrieval method, which may be helpful in attempts to develop a more uniformly standardized technique applicable to many different antigen systems.

Antigens, Neoplasm↗
PubMed1991

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↗
PubMedDate not supplied

Glassy cell carcinoma of the cervix: cytologic features and expression of estrogen receptor, progesterone receptor and Her2/neu protein.

OBJECTIVE: To analyze the cytologic features, estrogen and progesterone receptors, and Her2/neu protein in glassy cell carcinoma (GCC) of the cervix. STUDY DESIGN: Cases were analyzed using various parameters, including age at presentation, stage, treatment and clinical course. Between 1990 and 2003, patients with primary cervical carcinomas were treated and cytopathologic analyses performed. Tests for estrogen receptor (ER), progesterone receptor (PR) and Her2/neu protein were performed on paraffin sections. RESULTS: GCC of the cervix is composed of large cells with abundant chromatin, which gives them their characteristic glassy appearance. Eleven cases were identified as GCC. One case (9.1%) was correctly diagnosed from the cervicovaginal smear. Among the GCC cases, ER, PR and Her2/neu were positive in 2 (18.1%), 1 (9.1%) and 5 (45.4%) cases, respectively. CONCLUSION: Cytology of GCC reveals characteristic features that differ from those of other carcinomas of the cervix. GCC has unique cytologic characteristics and causes diagnostic confusion, possibly leading to incorrect diagnoses. The reason for such low diagnostic precision in cytology might be due to the lack of differentiation and low frequency of this tumor. Our results, demonstrating Her2/ neu overexpression, may correlate with more aggressive behavior and a worse clinical outcome.

Adult↗
PubMed2005

Roles of estrogen receptor, progesterone receptor, p53 and p21 in pathogenesis of pelvic organ prolapse.

The aim of this study is to compare the levels of estrogen receptor (ER), progesterone receptor (PR), p53 and p21 between pelvic organ prolapse (POP) and control groups in order to evaluate their roles in pathogenesis of POP, and to find out the relationship among these proteins. Through the year of 2002, uterosacral ligaments were obtained from 20 prolapsus and 24 non-prolapsus hysterectomized uteruses. ER, PR, p53, and p21 proteins were extracted by Western blot analysis and relative levels of proteins were compared by Student t-test and Pearson correlation coefficient. P value <0.05 was considered statistically significant. All patients were postmenopausal and had never taken hormone replacement therapy. ER, PR, p53, and p21 were significantly lower in the study than control group (p<0.0001). Positive correlations were found among all proteins in the prolapse group. Further researches are needed to elucidate the interrelationship among these proteins and their precise roles in pathogenesis of POP.

Aged↗
PubMed1990

Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause.

Estrogen receptors (ERs), progesterone receptors (PRs), and P29, an ER-associated protein, were studied immunohistochemically in human cervix with use of specific monoclonal antibodies. In ectocervical epithelium, homogeneous staining was found for P29 throughout the menstrual cycle and after menopause. Weak or moderate staining was found for ER in the basal and, occasionally, the parabasal layers of ectocervix during the proliferative phase. In contrast, staining decreased in secretory phase and postmenopausal epithelia. Staining was negative for PR in all the exocervical epithelia. Heterogeneous staining, more pronounced for P29, was found for the three antigens of the study in endocervical epithelium. Staining did not change with the hormonal status of patients, except for ER, where staining decreased during the secretory phase. Stromal cells were negative or weakly positive, whereas muscular fibers were positive. This study suggests that the capacity of response of the steroid apparatus of cervical cells to fluctuations of circulating estrogens and progestins is limited compared with some of the cell functions, such as mucus secretion, or with other target tissues, such as endometrium. Additionally, the differences found in the pattern of expression of the three antigens studied suggest that the steroid-dependent growth and differentiation in ectocervix is regulated differently to endocervix.

Biomarkers, Tumor↗
PubMed1999

Association of in vitro invasiveness and gene expression of estrogen receptor, progesterone receptor, pS2 and plasminogen activator inhibitor-1 in human breast cancer cell lines.

The invasive potential of tumor cells is usually tested either by in vitro invasion assays which evaluate cell spreading ability in basement membrane-like matrices or by in vivo invasion assays in nude mice. Both methods are laborious and time-consuming. Tumor invasiveness is accompanied by the changes in expression of various genes. The invasive behavior of cells is therefore represented by certain gene expression patterns. The purpose of this study was to investigate whether expression patterns of several genes are characteristic for the invasiveness of cultured cells. We examined the mRNA levels of estrogen receptor (ER), progesterone receptor (PR), estrogen inducible pS2 and plasminogen activator inhibitor-1 (PAI-1) in 23 cell lines derived from benign and malignant breast tissues using a competitive reverse transcription-polymerase chain reaction (cRT-PCR) system. We also evaluated the invasiveness of these cell lines by their ability to penetrate into a collagen-fibroblast matrix. We demonstrate that the gene expression pattern of breast cell lines is clearly associated with their in vitro invasiveness. In general, cells with ER, PR, pS2 but no PAI-1 expression showed a non-invasive phenotype, while cells expressing PAI-1 mRNA but not ER mRNA are invasive. Our study indicates that the invasiveness of breast cancer cell lines is characterized by PAI-1 gene expression and the lack of ER mRNA. This suggests that PAI-1 may participate in the invasive process.

Biomarkers, Tumor↗
PubMed1995

Effects of the pure anti-oestrogen ICI 182780 on oestrogen receptors, progesterone receptors and Ki67 antigen in human endometrium in vivo.

The new steroidal pure anti-oestrogen ICI 182780 was studied for the first time in pre-menopausal women. A total of 30 patients requiring hysterectomy for benign gynaecological disease were randomized to ICI 182780, 12 mg/day i.m. (n = 19) or no treatment (n = 11) for 7 days prior to surgery. Immunohistochemical measurements were made in the snap-frozen, resected endometrium for oestrogen receptors (ER), progesterone receptors (PgR) and Ki67, a nuclear antigen whose expression is closely related to proliferation. Five control patients ovulated prior to surgery and, as expected, the secretory endometria had lower Ki67 antigen concentrations than endometria had lower proliferative phase. The endometria from patients treated with ICI 182780 had reduced Ki67 compared with controls. This demonstration of reduced proliferative activity indicates that the pharmacological effectiveness of the treatment was maintained despite increased plasma oestradiol concentrations. In contrast to results from rodents, ICI 182780 did not markedly reduce ER expression, although there was significantly lower ER in the myometrial cells of the treated group. The lack of effect on PgR shows a dissociation between the drug's effect on this oestrogen-dependent protein and its effects on proliferation.

Adult↗
PubMed2002

Characterisation of oestrogen receptor, progesterone receptor, trefoil factor 1, and epidermal growth factor and its receptor in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: The pancreatic cystic neoplasms, including solid pseudopapillary tumour (SPT), mucinous cystic neoplasm (MCN), and intraductal papillary mucin producing tumour (IPMT), have their characteristic clinicopathological features. A systematic investigation of oestrogen receptor (OR), progesterone receptor (PR), trefoil factor 1(TFF1), and epidermal growth factor and its receptor (EGF and EGFR) expressed in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma was determined to elucidate their corresponding sex and age predilection, cell origin, and pathway of malignant transformation. METHODS: Surgical specimens of SPT (n=10), MCN (n=12), IPMT (n=10), and ductal adenocarcinoma (n=20) were studied. The expression of OR, PR, TFF1, EGF, and EGFR were each determined in each disease entity using monoclonal antibodies by immunohistochemical method. The results were correlated with the clinicopathological data. RESULTS: PR was expressed in all 10 SPT, whereas OR was expressed in none of 10 SPT. TFF1 was not or weakly expressed in SPT. Although EGF was strongly expressed in seven of 10 SPT, synchronous expression of EGF and its receptor was expressed in none of 10 SPT. Of the 12 MCN, six had PR expression in the stroma cells but not in the neoplastic epithelium, seven had a moderate or strong expression of TFF1, and 10 had no or weak EGFR expression, irrespective of their benigneity or malignancy. Synchronous expression of EGF and EGFR was observed in only one of 12 MCN. Among 10 IPMT, TFF1 and EGFR were moderately or strongly expressed in all six malignancies, whereas TFF1 and EGFR were not or weakly expressed in three of four benigneity. Of 20 ductal adenocarcinomas, TFF1 and EGFR were moderately or strongly expressed in 16 and 12, respectively. Synchronous expression of EGF and EGFR was observed in six of 10 IPMT and nine of 20 ductal adenocarcinoma, respectively. CONCLUSION: PR was uniquely expressed in SPT, and OR and PR were expressed in stroma of MCN, reflecting their sex and age predilection. TFF1 expression was related to EGFR such as in IPMT and ductal adenocarcinoma, not related to EGFR such as in MCN, and not related to hormonal receptors such as in SPT. EGF and its receptor might play a part in the malignant transformation of IPMT and ductal adenocarcinoma, but not of SPT and MCN.

Adult↗
PubMed2002

DNA aneuploidy in relation to the combination of analysis of estrogen receptor, progesterone receptor, p53 protein and epidermal growth factor receptor in 498 breast cancers.

BACKGROUND: Various studies have analyzed the relationships between new biological parameters and DNA ploidy for human cancer. However, the biological significance of DNA ploidy remains unclear, since there have so far been few studies analyzing DNA ploidy in relation to the combination of multiple such biological parameters. METHODS: Samples for the analysis of DNA ploidy, estrogen receptor (ER), progesterone receptor (PgR), p53 protein and epidermal growth factor receptor (EGFR) were prepared from the same frozen specimens of 498 primary breast cancers. DNA ploidy was determined by flow cytometry, while ER and PgR were determined by an enzyme immunoassay. Both p53 protein and EGFR were determined by immunohistochemical analyses. RESULTS: Aneuploidy was significantly correlated with the absence of ER, the absence of PgR, the positivity of p53 protein and the positivity of EGFR, and it was also significantly correlated with the combination of the absence of ER and PgR and the combination of the positivity of p53 protein and EGFR. A deviation in the four parameters was defined as the absence of ER, the absence of PgR, the positivity of p53 protein or the positivity of EGFR. As the number of deviations of these four biological parameters increased, the incidence of aneuploidy increased significantly (p < 0.0001). Multivariate analysis also indicated that deviation of two, three or all four parameters were significant factors for DNA ploidy, while the p value decreased and the odds ratio increased as the number of deviations of the four biological parameters increased. CONCLUSIONS: DNA aneuploidy based on flow cytometric analysis reflects the accumulation of deviations in the four biological parameters investigated in the present study. The two facts that DNA aneuploidy reflects the accumulation of the aggressiveness of these biological parameters and that DNA aneuploidy consisted of heterogeneous characteristics which were represented by the deviation of each biological parameter should be taken into consideration when selecting treatment strategies for breast cancer.

Adult↗