A subset of breast invasive ductal carcinoma with distinctive cytomorphology,aggressive clinical behavior,and unique immunologic profiles

BACKGROUND: Invasive ductal carcinoma of the breast is a heterogeneous collection of divergent types of carcinomas. Some subtypes have been characterized by histologic observations. This study describes a distinctive subset recognized through cytomorphologic examination of breast carcinoma specimens obtained by fine-needle aspiration biopsies (FNAB). Identification of this subset is established further by analyses of its clinical and immunologic characteristics. METHODS: One hundred patients underwent FNAB and were diagnosed with breast ductal carcinoma. These diagnoses were followed by surgical resections and histologic evaluation of tumors. Immunohistochemical analyses of estrogen receptor, progesterone receptor, Her2/neu, p53 protein, and Ki-67 were performed. Patient's age, race, and family history of breast carcinoma were obtained. The objective of the study is to identify a cytomorphologically distinctive, clinically relevant, subset of breast carcinomas. RESULTS: A subset carcinoma was recognized by cytomorphologic examination of Pap-stained FNAB slides. This subset consisted of seven patients with a median age of 37 years. At the time of surgical resection, all patients had axillary lymph node metastases. Six of seven patients had distant metastases. Immunohistochemical studies revealed that all tumors are positive for p53 protein and negative for estrogen and progesterone receptors. CONCLUSION: This study presented a unique subset of breast ductal carcinomas that involved young patients and had aggressive growth behavior. These tumors expressed p53 protein but not estrogen and progesterone receptors.     

Female sex steroid receptor status in primary and metastatic breast carcinoma and its relationship to serum steroid peptide hormone levels

In order to obtain more information on the interrelationships between cytosol estrogen (ER) and progestin (PR) receptors in breast carcinoma, and their distribution according to age, menopausal status and endocrine parameters of the patients, these receptors were measured in 605 primary and 150 metastatic lesions, and correlated with serum levels of estradiol, progesterone, FSH, LH and prolactin in some of these patients. Measurable estrogen receptor (> 3 fmol/mg cytosol protein) was found in 78.0% and progestin receptor (> 10 fmol/mg cytosol protein) in 60.5% of all the samples studied. The receptors were simultaneously present in 57.2%, estrogen receptor only in 20.8%, progestin receptor only in 3.3%, while both receptors were absent in 18.7% of the whole material. In samples from 253 premenopausal patients, measurable ER was found less frequently (71.1% of cases) and its concentration was lower (39.9 ± 5.1 fmol/mg cytosol protein, mean ± SEM) than in 502 postmenopausal patients (82%; 148.2 ± 11.6 fmol/mg). The frequencies of ER-positive samples and ER concentration were rather similar in primary and metastatic lesions, whereas PR was more often present (64 versus 47%) and its concentrations significantly higher (151.2 ± 12.5 versus 102.6 ± 21.1 fmol/mg) in primary than in metastatic tumors. When present simultaneously, there was a significant correlation between ER and PR concentrations in both primary and metastatic lesions independent of the menopausal status of the patient. ER concentration correlated significantly with age in both pre- and postmenopausal patients, while PR concentration correlated with age only in postmenopausal patients. The group with the highest ER values (above 100 fmol/mg cytosol protein) had a significantly lower serum estradiol concentration that the other patients. Serum estradiol values had a significantly positive correlation with cytosol PR content in the samples with a measurable PR. Serum progesterone, FSH, LH and prolactin did not correlate with tumor ER or PR concentrations. We conclude that concomitant assays of ER and PR from a breast carcinoma specimen provide a correct picture of the endocrine characteristics of the tumor independently of the serum concentrations of estradiol, progesterone, FSH, LH and prolactin.     

Immunohistochemical expression of hormone receptors and the histological characteristics of biochemically hormone receptor negative breast cancers

Background  Most of the discordant cases between biochemical and immunohistochemical (IHC) assays for hormone receptor (HR) status in breast cancers are due to negative findings from the biochemical assay but positive IHC findings. However determining HR status based on IHC only in biochemically HR negative breast cancers has never been studied. The aim of this study is to examine the histological characteristics in immunohistochemically HR positive but biochemically HR negative breast cancers. Methods  IHC staining for HRs in 345 biochemically HR-negative breast cancers was done. The relationship between HR status by IHC and the histological characteristics was assessed. Results  In 345 cancers, 105 (30.4%) were estrogen receptor- (ER) or progesterone receptor- (PR) positive by IHC. The enzyme-immunoassay (EIA) HR titer was higher in immunohistochemically HR-positive tumors (ER: 2.7 fmol/mg protein; PR: 0.8 fmol/mg protein) than in negative tumors (0.6 fmol/mg protein in both HRs). IHC-assessed ER positivity on histological sections was high in some tumor types, such as mucinous carcinoma (77.8%), invasive micropapillary carcinoma (66.7%), and infiltrating ductal carcinoma of no special type with abundant stroma (60.2%). Among infiltrating ductal carcinomas of no special type, low nuclear grade tumors were all ER positive and high nuclear grade tumors showed low ER positivity by IHC, even in biochemically HR negative cancers. Conclusion  The IHC-assessed HR status may reflect tumor cell behavior, such as overall and disease-free survival and endocrine response, better than HR status as assessed by the enzyme-immunoassay method. Immunohistochemically HR-positive but biochemically HR-negative breast cancers include infiltrating ductal carcinomas of no special type with low nuclear grade and some tumor types with high stromal content. We can assess the true HR status by IHC especially these tumors.     

Histological and immunohistochemical analysis of apocrine breast carcinoma

BACKGROUND: There are few data regarding the biological characteristics of apocrine breast carcinoma in the literature due to its rarity and controversy over its definition. We analyzed the histopathological characteristics and tumor biology of apocrine breast carcinomas with regard to histological grade, p53, HER2, bcl-2, MIB-1 and hormone receptor status. PATIENTS AND METHODS: A consecutive series of 24 female apocrine breast carcinoma patients were the primary source of these retrospective data. Background factors including histological grade, nodal status and lymphatic invasion by tumor cells were analyzed. Immunohistochemical staining for p53, HER2, MIB-1, bcl-2, estrogen receptor (ER) and progesterone receptor (PR) was carried out on formalin-fixed, paraffin embedded specimens. RESULTS: Older age and postmenopausal status were observed more frequently in patients with apocrine breast carcinoma than those with invasive ductal carcinoma. Apocrine breast carcinoma also showed relatively lower histological grade than invasive ductal carcinoma. Nuclear accumulation of p53, HER2 overexpression, bcl-2 and MIB-1 index were observed in 29% (7/24), 33%(8/24), 25%(6/24) and 29% (7/24) of cases, respectively. Positivity for ER and PR was present in 17% (4/24) and 17% (4/24) of cases, respectively. CONCLUSIONS: Apocrine breast carcinoma tended to show low MIB-1 index, low bcl-2 expression and low positive rate of hormone receptors. There was no correlation between the three types of apocrine carcinoma and the positivity rate of p53, HER2, bcl-2, MIB-1 and hormone receptor status.     

The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen.

Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer.     

c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma.

c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors, while the level of expression in normal breast tissue was much less than that in breast cancer. Membrane staining of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11 normal breast tissue samples was positive. The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation marker were compared with lymph node status, estrogen receptor status, progesterone receptor status, and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status. We concluded that they might be additional prognostic factors for breast carcinoma.     

P53 expression in breast cancer

Immunohistochemical evaluation of 200 primary breast cancers with the anti-p53 mouse monoclonal antibody (MAb) PAb421 showed positivity in nuclei of malignant cells in 31 cases (15.5%). PAb421+ cases were significantly more frequently epidermal growth factor receptor (EGF-R)-positive (67.7%; p less than 0.001) and estrogen receptor (ER)-negative (73.3%; p less than 0.001); they displayed surface histocompatibility class-1 (80.6%; p less than 0.01) and 11 (74.2%; p less than 0.05) antigens. Low values for progesterone receptor (mean 67.20 +/- 25.2 fmol/mg; p less than 0.05) and a high number of cells positive for the proliferation-associated antigen Ki-67 (log mean 6.88 +/- 0.33; p less than 0.01) were found in PAb421+ tumors as well as a high number of grade-3 infiltrating duct carcinomas (70%; p = 0.01). Of the 200 cases of mammary carcinoma, 88 were further analyzed using another human specific anti-p53 MAb PAb1801, and 40 (45.5%) were found positive. This MAb stained all the PAb421+ cases and was significantly associated with negative ER status (39.5%; p less than 0.05) and high Ki-67 scores (log mean 6.93 +/- 0.24; p = 0.001). Analysis of PAb1801+/Pab421- cases for HLA antigens, EGF-R and ER showed a phenotype similar to that of the p53-ve/ER+ carcinomas, except for the high Ki-67 score. No differences in age of the patient, number of involved nodes, tumor size, ploidy or labelling index scores were evident between p53+ and carcinomas. We concluded that p53 in mammary carcinomas is associated with ER-negative, growth factor receptor-positive, high-grade tumors, and is a promising new parameter to evaluate the cellular biology and prognosis of breast cancer.     

Tamoxifen-induced progesterone receptors in breast tumors]

Estrogen and progesterone receptors were assayed in 86 patients with breast cancer following 7-day treatment with 20 mg tamoxifen. The results were compared with the data on the receptor status of 127 untreated patients with breast cancer. Mean progesterone receptor level was significantly increased whereas that of estrogen receptors was significantly decreased in patients aged 20-49 and 60-69 years. It is suggested that tumors in which stimulated progesterone receptor level is higher than 50 fmol/mg protein be considered hormone-dependent.     

Prognostic Significances of Estrogen and Progesterone Receptors in Primary Operable Breast Cancer

Both estrogen and progesterone receptors have been determinedin 613 primary breast cancer patients treated by radical mastectomy.At the cut-off value of 5 fentomoles (fmol) cytosol pro-tein/mgfor both receptors, patients with estrogen or progesterone receptor-positivebreast cancer showed significantly favorable disease-free, overalland post-recurrence survival curves to those of receptor-negativebreast cancer patients. In the patient subgroups: premenopausal,stage III, more than four positive lymph node metastases, postoperativeadjuvant tamoxifen therapy, a significantly favorable prognosiswas recognized in either estrogen or progesterone receptor-positivepatients. Both receptors are thought to be useful prognosticindicators for patients with advanced tumors or for those receivingpostoperative adjuvant tamoxifen therapy. When the cut-off valuewas changed, the maximum significant difference in prognosisbetween receptor-positive and receptor-negative patients wasobserved at 5 fmol cytosol protein/mg for the estrogen receptoror 10 fmol/mg cytosol protein for the progesterone receptor.A more detailed examination should be made on the cut-off valuesof both receptors.     

Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer

Levels of epidermal growth factor receptor (EGF-R) and insulin-like growth factor receptor (IGF-R) in breast cancer tissue were evaluated. The binding of growth factors was compared to the content of estrogen receptors (ER) and progesterone receptors (PgR). EGF-R correlated negatively to the ER and PgR (Kendall correlation, P less than 0.001), whereas the IGF-R correlated positively to ER and PgR (analysis of variance, P less than 0.001). In contrast, no correlation was found between EGF-R and IGF-R. IGF-R binding was higher in tumor tissues than in adjacent normal tissues (Wilcoxon rank test, P less than 0.001), whereas the EGF-R binding in normal tissue did not differ from that in cancer tissue. The degree of differentiation in ductal breast cancer correlated to EGF-R (chi 2 test, P = 0.018), but not to IGF-R. The bindings of both growth factors were the same in metastases and primary breast tumors. Our results show that EGF-R and IGF-R are present in normal breast tissue and breast cancer tissue. The growth factor receptors are related to steroid receptor content and their presence is associated with malignant transformation of breast cells and dedifferentiation of breast cancer.     

散发性乳腺浸润性导管癌中BRCA1 表达及临床意义*

目的:研究散发性乳腺浸润性导管癌（invasive ductal carcinoma,IDC）（breastcancer 1 BRCA1）基因的表达及其与其临床病理特征之间的关系。方法:采用免疫组化SP三步法检测67例乳腺浸润性导管癌,53例乳腺腺病患者的石蜡标本BRCA1 的表达,从病理科的档案提取患者的年龄,肿物大小,淋巴结转移情况,ER,PR,Her-2 表达结果,分析BRCA1 的表达和患者的年龄,肿物大小,淋巴结转移情况及ER,PR,Her-2 表达的关系。结果:BRCA1蛋白在IDC 组织表达率56.7%（38/67）,癌旁组织表达率80.0%（36/45）,乳腺腺病组织表达率92.5%（49/53）。 阳性细胞定位除细胞核外,也见于胞浆。IDC 癌组织与癌旁组织、乳腺腺病组织比较,BRCA1 阳性表达率均下降,均有显著性差异（P<0.05）。 BRCA1 的表达与淋巴结转移呈负相关（r=-0.137,P<0.05）,与ER、PR、Her-2 的表达均呈负相关（r 值分别为-0.439,-0.250,-0.363,P<0.05）,与年龄、肿物大小无明显相关性（P>0.05）。 结论:BRCA1 蛋白可作为估计乳腺癌生物学行为和预后的潜在指标。      

The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma

AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS: The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated positively with histological grade and Ki-67 expression (P < 0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant. CONCLUSION: In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.     

Predictive value of tumor estrogen and progesterone receptor levels in postmenopausal women with advanced breast cancer treated with toremifene

The predictive value of estrogen receptor (ER) concentrations was evaluated in a group of 113 postmenopausal patients with estrogen-receptor-positive (ER greater than 7 fmol/mg protein) advanced breast cancer. In 103 patients, tumors were also sampled for progesterone receptor (PgR) determination. All patients were treated with toremifene, a novel antiestrogen, 60 mg daily. The median ER in 51 responders was 78 fmol/mg protein, and in 62 nonresponders, 51 fmol/mg protein; the median PgR levels were 40 and 37 fmol/mg protein, respectively. The response rate in patients with ER less than 50 fmol/mg protein was 38%, and 51% in the group with ER greater than 50 fmol/mg protein (not significant [NS]). The response rate in patients with PgR less than 10 fmol/mg protein was 42%, and in patients with greater than 10 fmol/mg protein, 44%. The duration of response in patients with ER greater than 50 fmol/mg protein was significantly longer than with lower ER levels (P = 0.002). PgR was not associated with the duration of response. In Cox's multiple regression analysis, ER was an independent prognostic factor (P = 0.005) for response duration. Thus, the ER concentration of tumor tissue predicts the duration of response but not the response rate to toremifene in patients with advanced breast cancer. The PgR status does not predict the response rate or the duration of response.     

A case of ductal adenoma of the breast which contains high-concentration of steroid-hormone receptors

A case of ductal adenoma of the breast in a 64-year-old Japanese woman is reported. The patient presented with a well-defined, 0.9 cm, firm mass in the right breast. Histological examination of the excised tumor revealed small and medium-sized ductules forming a nodular pattern partly surrounded by a thin layer of mature collagenous fibers. A few hyalinized fibers were also observed among the ductules, which had a clearly defined basement membrane, diagnosed as ductal adenoma of the breast. Determination of steroid hormone receptor by a dextran-coated charcoal method revealed that the ductal adenoma contained high concentration of estrogen receptor (ER) and progesterone receptor (PgR) (280 and 105 fmol/mg protein, respectively). The patient had a previous history of invasive ductal carcinoma of the left breast and had undergone a modified radical mastectomy 4 years earlier. The contralateral breast cancer was also positive for both ER and PgR (350 and 78 fmol/mg protein, respectively).     

Epidermal growth factor receptor in human breast cancers: Correlation with estrogen and progesterone receptors

Epidermal growth factor receptor (EGFR), determined by the Scatchard curve method, was found in 22 cases of a random series of 100 patients with breast carcinoma. Two groups of patients were identified, one (n = 16) with a low concentration (0–50 fm/mg protein) of EGFR but with a high affinity (Kd = 3.2 nM), and the other (n = 6) with a high concentration (90–210 fm/mg protein) of EGFR but with a lower affinity (Kd = 6.3 nM).A significant inverse relationship was found between the presence of EGFR and receptors for estrogen (p<0.001) and progesterone (p = 0.001). EGFR was found in no (0/8) tumors with Grade I histoprognostic grade, 17% (10/58) Grade II, and 38% (11/29) Grade III (p<0.05). EGFR is present therefore in poorly differentiated tumors and associated with other factors of poor prognosis. Ourin vivo analyses confirm results found in tissue culture derived from human breast carcinoma cells.With the technical assistance of J. Barraque.     

Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer.

The distribution and frequency of steroid hormone receptors are described 329 patients with breast cancer. The distribution of each of the steroid hormone receptors is unimodal with a progressive increase in the proportion of patients positive at lower receptor values. Receptor values expressed as fmol/mg cytoplasmic protein are well correlated with values expressed as fmol/mg breast tumor. Estrogen receptor was positive in 53% of the patients; progesterone receptor was positive in 38% of the patients; glucocorticoid receptor was positive in 52% of the patients; and androgen receptor was positive in 31% of the patients. The type of tissue assayed did not affect steroid hormone receptor positivity. For primary tumors, there was no correlation between steroid hormone receptor positivity and location of the tumor in the breast, size of the tumor, or extent of the disease. Each of the steroid hormone receptors was positively associated with each of the other steroid hormone receptors. Estrogen receptor was correlated with menopausal status and axillary nodal status, but these correlations did not exist for the other steroid hormone receptors. Estrogen receptor was not correlated with age after adjustment for menopausal status. The other steroid hormone receptors were not correlated with age.     

乳腺浸润性导管癌18F-FDG摄取的影响因素分析

目的:探讨肿瘤大小、病理分级、有无淋巴结转移及病理分子标志物雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体(C-erbB-2)、p53抑癌基因(p53)及增殖细胞核抗原Ki67(Ki67)对乳腺浸润性导管癌18F-FDG摄取的影响。方法:37例病理证实乳腺浸润性导管癌术前18F-FDG PET/CT SUVmax与术后病理免疫组化结果进行综合分析,采用Mann-Whitney U检验进行统计学分析。结果:病灶直径≥2.5cm、肿瘤高分化(III级)、淋巴结转移组平均SUVmax分别高于<2.5cm、低分化(I-II级)及淋巴结未转移有统计学意义(P<0.05)。ER(﹣)组18F-FDG摄取程度高于ER(﹢)组(P<0.05),Ki67(﹢)组18F-FDG摄取程度高于Ki67(﹣)组,差异均有统计学意义(P<0.05)。而PR、C-erbB-2及p53对18F-FDG摄取影响不明显。结论:乳腺浸润性导管癌病灶大小、病理分级、有无淋巴结转移、ER、Ki67的表达影响18F-FDG摄取,18F-FDG PET/CT鉴别诊断及初步分期时应引起重视。     

Hormone receptors in male breast carcinoma

It is well established that approximately 60% of female breast cancers contain estrogen receptors (ER+). The hormonal receptor status of male breast cancers remains relatively unknown. Tumor tissue from 14 patients has been reviewed at the University of Oregon Health Sciences Center. Specimens of all 14 patients were ER+ with a range of 5.5 to 374 fmol/mg protein. Eight of 12 patients had tumors which also contained progesterone receptors (PR+) with a range of 42 to 1852 fmol/mg protein. Nine patients were treated by modified radical mastectomy, two by radical mastectomy, one by simple mastectomy, and two by biopsies only. Twelve patients remain free of disease with a mean follow-up of less than 2 years. The two patients who developed metastases both responded to endocrine ablation by orchiectomy and subsequent adrenalectomy. These data suggest that male breast cancer is highly endocrine sensitive and that endocrine ablation can play an integral part in those men unfortunate enough to develop disseminated disease.     

p53 protein overexpression in infiltrating ductal carcinoma of female breast and its association with lymph node metastasis

Traditionally, prognosis in carcinoma of the breast is evaluated based on size and differentiation of the tumor and status of lymph node metastasis. In addition to these established markers, in this molecular age other parameters such as overexpression of p53, c-erbB-2 and c-myc proteins are increasingly used to assess the prognosis. At present, the prognostic value of the molecular markers, at best, is controversial and conflicting. In this study, we examined 67 infiltrating ductal. carcinomas of female breast with and without lymph node metastasis for p53 protein overexpression by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections to ascertain if p53 positive tumors have greater metastatic potential than p53 negative tumors. In addition, p53 overexpression was also correlated with tumor size, grade, expression of estrogen and progesterone receptors, and age of the patient to clarify the issue of relevance of p53 overexpression in prognostication, p53 overexpression was observed in 39% of tumors and showed strong correlation only with the histological grade of the tumor. The incidence of p53 overexpression in grade 1, grade 2 and grade 3 tumors was 0%, 33% and 58% respectively. Lymph node metastasis was less frequent in tumors that overexpressed p53 protein. Twenty-seven percent of primary tumors with lymph node metastasis showed p53 protein overexpression, in contrast to 44% of tumors without metastasis. No correlation was observed between p53 overexpression and all the other parameters evaluated except progesterone receptor negative status. These results suggest that p53 overexpression is not an independent prognostic indicator and should not be used to predict lymph node metastasis or aggressive behavior of the tumor.     

Plasminogen activator as a functional marker for estrogen dependence in human breast cancer cells

To examine whether plasminogen activator reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors, such as cytoplasmic estrogen receptor (ERC), progesterone receptor (PgR) and nuclear estrogen receptor (ERN). With any receptor, plasminogen activator activity was significantly higher in receptor-positive tumors than in receptor-negative tumors. When these breast tumors were categorized into 8 groups in terms of combinations of receptor status, breast cancers which were positive for all these receptors were found to contain the highest plasminogen activator activity. Furthermore, quantitative analyses demonstrated positive correlations of the enzyme activity with either ERC content (correlation coefficient +0.37, P less than 0.001) or PgR content (correlation coefficient +0.45, P less than 0.001). These results strongly suggest that plasminogen activator can be used as an effective functional marker for hormone dependence in human breast cancer.