Oestrogen receptor co-activator AIB1 is a marker of tamoxifen benefit in postmenopausal breast cancer.

BACKGROUND: The oestrogen receptor (ER) co-activator amplified in breast cancer 1 (AIB1) has been suggested as a treatment predictive and prognostic marker in breast cancer. Studies have however not been unanimous. PATIENTS AND METHODS: AIB1 protein expression was analysed by immunohistochemistry on tissue micro-arrays with tumour samples from 910 postmenopausal women randomised to tamoxifen treatment or no adjuvant treatment. Associations between AIB1 expression, clinical outcome in the two arms and other clinicopathological variables were examined. RESULTS: In patients with ER-positive breast cancer expressing low tumour levels of AIB1 (<75%), we found no significant difference in recurrence-free survival (RFS) or breast cancer-specific survival (BCS) between tamoxifen treated and untreated patients. In patients with high AIB1 expression (>75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26-0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21-0.69, P = 0.0015) with tamoxifen treatment. In the untreated arm, we found high expression of AIB1 to be significantly associated with lower RFS (HR 1.74, 95% CI 1.20-2.53, P = 0.0038). CONCLUSION: Our results suggest that high AIB1 is a predictive marker of good response to tamoxifen treatment in postmenopausal women and a prognostic marker of decreased RFS in systemically untreated patients.

Ultrasound for diagnosing acute salpingitis: a prospective observational diagnostic study.

STUDY QUESTION: What are the diagnostic benefits of using ultrasound in patients with a clinical suspicion of acute salpingitis and signs of pelvic inflammatory disease (PID)? SUMMARY ANSWER: In patients with a clinical suspicion of acute salpingitis, the absence of bilateral adnexal masses at ultrasound decreases the odds of mild-to-severe acute salpingitis about five times, while the presence of bilateral adnexal masses increases the odds about five times. WHAT IS KNOWN ALREADY: PID is difficult to diagnose because the symptoms are often subtle and mild. The diagnosis is usually based on clinical findings, and these are unspecific. The sensitivity and specificity of ultrasound with regard to salpingitis have been reported in one study (n = 30) of appropriate design, where most patients had severe salpingitis (i.e. pyosalpinx) or tubo-ovarian abscess. STUDY DESIGN, SIZE, DURATION: This diagnostic test study included 52 patients fulfilling the clinical criteria of PID. Patients were recruited between October 1999 and August 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients underwent a standardized transvaginal gray scale and Doppler ultrasound examination by one experienced sonologist (index test) before diagnostic laparoscopy by a laparoscopist blinded to the ultrasound results. The final diagnosis was determined by laparoscopy, histology of the endometrium and other histology where relevant (reference standard). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 52 patients, 23 (44%) had a final diagnosis unrelated to genital infection, while the other 29 had cervicitis (n = 3), endometritis (n = 9) or salpingitis (n = 17; mild n = 4, moderate n = 8, severe, i.e. pyosalpinx n = 5). Bilateral adnexal masses and bilateral masses lying adjacent to the ovary were seen more often on ultrasound in patients with salpingitis than with other diagnoses (bilateral adnexal masses: 82 versus 17%, i.e. 14/17 versus 6/35, P = 0.000, positive likelihood ratio 4.8, negative likelihood ratio 0.22; bilateral masses adjacent to ovary: 65 versus 17%, i.e.11/17 versus 6/35, P = 0.001, positive likelihood ratio 3.8, negative likelihood ratio 0.42). In cases of salpingitis, the masses lying adjacent to the ovaries were on average 2-3 cm in diameter, solid (n = 14), unilocular cystic (n = 4), multilocular cystic (n = 3) or multilocular solid (n = 1), with thick walls and well vascularized at colour Doppler. In no case were the cogwheel sign or incomplete septae seen. All 13 cases of moderate or severe salpingitis were diagnosed with ultrasound (detection rate 100%, 95% confidence interval 78-100%) compared with 1 of 4 cases of mild salpingitis. Three of six cases of appendicitis, and two of two ovarian cysts were correctly diagnosed with ultrasound, and one case of adnexal torsion was suspected and then verified at laparoscopy. LIMITATIONS, REASONS FOR CAUTION: The sample size is small. This is explained by difficulties with patient recruitment. There are few cases of mild salpingitis, which means that we cannot estimate with any precision the ability of ultrasound to detect very early salpingitis. The proportion of cases with salpingitis of different grade affects the sensitivity and specificity of ultrasound, and the sensitivity and specificity that we report here are applicable only to patient populations similar to ours. WIDER IMPLICATIONS OF THE FINDINGS: The information provided by transvaginal ultrasound is likely to be of help when deciding whether or not to proceed with diagnostic laparoscopy in patients with symptoms and signs suggesting PID and, if laparoscopy is not performed, to select treatment and plan follow-up.

Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial.

BACKGROUND: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. METHODS: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomised prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modelling. RESULTS: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorised as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorised as low risk with an 8.3% 10-year distant recurrence risk. CONCLUSION: Retrospective analysis of this randomised, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.

Immunocytochemistry: an indispensable technique in routine cytology.

Immunocytology is today accepted as an indispensable adjunct to cytomorphology. It has led to a dramatic increase in diagnostic accuracy and also allowed the identification of markers both for prognosis and targeted therapies. Most commercially available antibodies will perform in a reproducible and reliable way provided that the cytological specimen has been prepared and fixed properly. In this review various aspects of immunocytochemistry such as preparation of cytological specimens, fixation and choice of antibodies will be discussed. The specificity of the most commonly used antibodies is summarized and staining panels for various tumours are suggested. In addition, the use of markers for targeted therapy and theranostics is discussed, as well as a brief section on the identification of infectious agents.

Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) lacking expression of steroid receptors and human epidermal growth factor receptor 2, having chemotherapy as the only therapeutic option, is characterised by early relapses and poor outcome. We investigated intratumoural (i.t.) levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF) and survival in patients with TNBC compared with non-TNBC. PATIENTS AND METHODS: VEGF levels were determined by an enzyme immunosorbent assay in a retrospective series consisting of 679 consecutive primary breast cancer patients. RESULTS: Eighty-seven patients (13%) were classified as TNBC and had significantly higher VEGF levels; median value in TNBC was 8.2 pg/microg DNA compared with 2.7 pg/microg DNA in non-TNBC (P < 0.001). Patients with TNBC had statistically significant shorter recurrence-free survival [hazard ratio (HR) = 1.8; P = 0.0023], breast cancer-corrected survival (HR = 2.2; P = 0.004) and overall survival (HR = 1.8; P = 0.005) compared with non-TNBC. Patients with TNBC relapsed earlier than non-TNBC; mean time from diagnosis to first relapse was 18.8 and 30.7 months, respectively. The time between first relapse and death was also shorter in TNBC: 7.5 months versus 17.5 months in non-TNBC (P = 0.087). CONCLUSIONS: Our results show that TNBC have higher i.t. VEGF levels compared with non-TNBC. Ongoing clinical trials will answer if therapy directed towards angiogenesis may be an alternative way to improve outcome in this poor prognosis group.

Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer.

The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1, assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1-amplified tumors, indicating coamplification (P<0.001). In ER-positive patients, amplification of at least one of the genes indicated a reduced recurrence-free survival (P=0.025). When response to tamoxifen treatment was analysed, patients with PAK1 amplification showed decreased benefit from the drug (ER+; relative risk ratio (RR)=1.62; 95% confidence interval (CI), 0.47-5.55) compared to patients without amplification (ER+; RR=0.53; 95% CI, 0.32-0.88). This was not evident for CCND1 amplification. We show that PAK1 may be a predictor of tamoxifen resistance and furthermore, we do not discard PAK1 as a potential candidate oncogene in the 11q13 amplicon. In addition, we show that high pak1 protein levels may predict tamoxifen insensitivity.

The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology.

BACKGROUND: Progestins as well as estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of mifepristone on cell proliferation in human breast tissue in vivo was studied in premenopausal women. METHODS: A group of 30 women, scheduled for surgical treatment of leiomyomas, were randomized to either 50 mg mifepristone or placebo every other day, for 3 months. Fine needle aspiration biopsies were obtained at baseline and after 3 months. Immunocytochemical analysis of Ki-67 was performed to reflect breast epithelial cell proliferation. Samples from 14 women were included in the final analyses. RESULTS: The Ki-67 index was significantly reduced after mifepristone treatment compared with baseline (P = 0.012). Furthermore, less individual variation in the Ki-67 index was seen in the mifepristone group. Treatment with mifepristone did not affect cortisol levels, whereas an increase in serum testosterone was noted. Breast symptoms like soreness and swelling were reduced, whereas the incidence of flushes increased. CONCLUSIONS: The ability of mifepristone to block breast epithelial cell proliferation in premenopausal women may prove beneficial when used for contraceptive purposes or for other gynaecological indications. Future studies should address a possible antiproliferative effect in the post-menopausal breast tissue during hormone replacement therapy. Our results implicate a possible protective effect of mifepristone on the breast epithelium. ClinicalTrials.gov NCT00579475.

Case report: Calcium pyrophosphate dihydrate deposition of the temporomandibular joint diagnosed by fine-needle aspiration cytology.

Calcium pyrophosphate dihydrate deposition (CPDD) is the accepted name for a disease that mainly occurs in elderly patients. This disease affects many joints in particular the knee joint. CPDD is extremely rare in the temporomandibular joint (TMJ) with only few cases reported in the English literature. Herein, we present a case of an 89 years old woman with a radiological diagnosis of chondrosarcoma of TMJ. Fine-needle aspiration cytology however showed crystals, multinucleated giant cells and macrophages which allowed a correct diagnosis of CPDD.

Expression of syndecan-1 in paired samples of normal and malignant breast tissue from postmenopausal women.

BACKGROUND: The mammary stroma is important for modulating epithelial breast cell response to sex steroid hormones. Proteoglycans, such as syndecan-1, promote the integration of cellular signals. MATERIALS AND METHODS: The immunohistochemical expression of syndecan-1 and of the androgen receptor (AR) was analyzed in paired samples of cancer and adjacent normal tissue from postmenopausal women. RESULTS: Normal and cancer tissue showed dramatic differences in the expression of syndecan-1. In malignant breast stroma, mean values were more than 10-fold higher than in normal tissue (p<0.001). There was also a marked redistribution from the epithelium to the stroma. The expression of AR was on average 2-fold higher in cancerous than in normal tissue (p<0.01). CONCLUSION: Breast cancer patients have very different prognoses. Syndecan-1 and the AR may be new molecular markers relevant to clinical outcome. The redistribution from the epithelium and the dramatic increase of syndecan-1 in cancerous stroma may be related to the natural history of the disease.

Dietary habits and prognostic factors in breast cancer.

The relationship between dietary habits and prognostic factors for breast cancer was studied in 240 women aged 50-65 years who had surgery for breast cancer between 1983 and 1986. A dietary history interview was conducted within the 4 months following resection of the primary tumor. In the stepwise multivariate analysis, the multiple-odds ratio (OR) for having a tumor greater than or equal to 20 mm in diameter was 0.95 (95% confidence interval, 0.91-0.99) for each 1-g increase in fiber intake per 10 MJ of energy intake. Compared with patients having tumors poor in estrogen receptor (ER), those having ER-rich tumors (greater than or equal to 0.10 fmol/microgram of DNA) were older (P less than .01) and reported carbohydrate intake yielding higher E% (percentage of total energy intake) (P less than .01) and higher retinol intake per 10 MJ (P less than .05). The OR for having an ER-rich tumor was 1.58 (95% confidence interval, 1.08-2.31) for each 1-mg increase in retinol intake per 10 MJ; 1.09 (95% confidence interval, 1.02-1.16) for each additional year of age; and 1.08 (95% confidence interval, 1.02-1.13) for each 1% increment in E% from carbohydrates. These results suggest that the dietary patterns of the western world (e.g., high fat intake and low intake of carbohydrates and fiber) affect certain prognostic factors in breast cancer, such as tumor size and ER content of the tumor.

Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy.

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related decrease of ultraviolet light-induced DNA repair synthesis in human peripheral leukocytes.

The capacity for ultraviolet light-induced DNA repair synthesis, studied in peripheral leukocytes from 58 healthy subjects 13 to 94 years old, was found to vary greatly between individuals. A negative, statistically significant correlation was obtained between age and this synthesis, indicating a decrease in repair capacity with age. An age-related decrease in DNA repair may increase the susceptibility of cells to agents causing DNA damage, i.e. carcinogens and certain cytostatic drugs.

Deletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases.

Genetic alterations that occur in human breast cancers are believed to be of importance for initiation as well as progression of the disease. In order to find a genetic alteration that may be used as a prognostic marker, 82 familial breast carcinomas were analyzed for loss of constitutional heterozygosity at polymorphic loci on all chromosomes. Frequently occurring allele losses were compared to estrogen receptor expression, lymph node metastases, tumor size at the time of operation, and distant metastases at the time of follow-up 2-15 years later. Loss of heterozygosity (LOH) on the long arm of chromosome 16 in the tumor at the time of operation was significantly correlated (P < 0.001) with the occurrence of distant metastases 1-13 years after the operation. In addition, LOH at 16q was not correlated with estrogen receptor status, lymph node positivity, or tumor size, nor was the occurrence of distant metastases correlated with any of these parameters. The results suggest the existence of a tumor suppressor gene on 16q that facilitates hematogenic spread of breast cancer and that LOH at this locus is an independent prognostic marker in breast cancer.

Loss of heterozygosity in familial breast carcinomas.

Three loci have been implicated in the etiology of familial breast cancer; the BRCA1 locus on 17q, the p53 gene on 17p, and the androgen receptor gene on the X chromosome. However, it has been estimated that in approximately 50% of all breast cancer families the predisposing genetic defect is not linked to any of these three loci. In an attempt to identify chromosomal regions harboring putative breast cancer genes we performed allelotyping in 82 familial breast carcinomas. Polymorphic markers representing 45 different loci were analyzed and the most frequently involved chromosomal arms were 8p, 16q, 17p, 17q, and 19p.

Influence of genotype and the organ of origin on the subtype of T-cell in Moloney lymphomas induced by transfer of preleukemic cells from athymic and thymus-bearing mice.

Thymus, spleen, and bone marrow of 1-month-old neonatally Moloney murine leukemia virus-inoculated mice have been transferred to 400-R-irradiated syngeneic recipients of the opposite sex. The donor or recipient origin of T-cell lymphomas arising in the host animal was identified by the sex chromosome marker. Spleen and bone marrow of athymic BALB-nu/nu mice contain cells with the potential to develop into T-cell lymphomas upon transfer to thymus-bearing BALB/c recipients. Such lymphomas arise from at least two subsets of T-cells, one terminal deoxynucleotidyl transferase (TdT) positive and the other 20 alpha-hydroxysteroid dehydrogenase positive. The enzyme-negative precursor T-cells from the BALB-nu/nu spleen and bone marrow can thus mature to enzyme-positive cells and give rise to lymphoma in the thymus-bearing recipient. Preleukemic spleen and bone marrow, but not thymus, from CBA and BALB/c mice regularly contained cells with the potential to develop lymphoma. The subset of T-cell involved was influenced by the genotype since lymphomas arising after the transfer of CBA and BALB/c spleens were TdT positive and 20 alpha-hydroxysteroid dehydrogenase positive, respectively. In thymus-bearing mice, but not in nude mice, the transfer of preleukemic spleen cells gave lymphomas earlier than did transfer of bone marrow cells. This suggests that the more mature lymphoid cell population in the spleen of thymus-bearing mice may allow leukemic transformation to occur more rapidly than do the less mature cells in the bone marrow. In one-third of the cases, the virus produced by the preleukemic cells transferred induced new lymphomas involving recipient host cells. These de novo-induced lymphomas were all TdT positive. We suggest that leukemic transformation of TdT-positive cells may occur through a different mechanism than does transformation of cells bearing the 20 alpha-hydroxysteroid dehydrogenase marker.

Deletion mapping of chromosome 8p in prostate cancer by fluorescence in situ hybridization.

Double-target fluorescence in situ hybridization (FISH) was applied to 42 cases of prostate cancer and seven cases of histologically proven benign prostate hyperplasia for the detection of structural aberrations of chromosome 8. Cosmid probes for two chromosome 8p loci (LPL/8p22 and D8S7/8p23) were used in 34 specimens of malignant tumors obtained by the touch biopsy technique. Deletion was defined as when the number of cosmid signals was lower than the number of centromere signals in more than 35% of all nuclei observed. In total, thirty of the 42 (71%) specimens demonstrated any type of 8p deletion. Out of the 34 cases in which deletion mapping could be evaluated, distal deletion (D8S7) was detected in 17 (50%), of which 10 also showed deletion of LPL. Deletion of LPL was detected in 18 cases (53%), of which 8 (24%) retained the D8S7 (interstitial deletion). When the deletion pattern was graded as (1) no deletion (2) partial deletion (either D8S7 or LPL deleted) and (3) both deletions, the degree of deletion was well correlated with the tumor grade (P = 0.0009) and with stage (P = 0.0072, Fisher's Exact test). These data support the hypothesis that tumor suppressor gene(s) may be located in the chromosomal region 8p22, hence 8p deletions may play a crucial role in the pathogenesis of prostate cancer.

Adjuvant tamoxifen in early-stage breast cancer: effects on intercurrent morbidity and mortality.

Intercurrent mortality and the pattern of inpatient hospital care was studied among 1,846 postmenopausal patients included in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy. The median follow-up time was 54 months (range, 2 to 123 months). The patients were matched to the Swedish National Registry of Causes of Death and a computerized register covering about 95% of all hospital admissions in Stockholm County. There was no significant difference in the pattern of intercurrent mortality among the tamoxifen and control patients. The total number of hospital admissions was similar in both groups, but the tamoxifen patients were admitted significantly less frequently because of immunologic diseases (relative risk [RR] = 0.4; 95% confidence interval [CI], 0.2 to 0.9). Admissions because of thrombotic diseases were slightly, but not significantly, more frequent among the tamoxifen patients (RR = 1.2; 95% [CI], 0.6 to 2.3). The risk of hospital stay for benign gynecologic diseases other than prolapse or uterine bleeding was increased in the tamoxifen group (RR = 3.2; 95% CI, 1.2 to 8.6). No significant differences were found for diseases related to arteriosclerosis or osteoporosis. The study confirms and extends previous reports, which have shown that tamoxifen has few and usually mild side effects. However, the current results should be judged cautiously because of the relatively short median follow-up time (4.5 years) and the limitation of data in detecting morbidity that does not necessarily result in hospitalization.

S-phase fraction is a prognostic factor in stage I breast carcinoma.

PURPOSE AND METHODS: The prognostic significance of cell proliferation, estimated as cytometric S-phase fraction (SPF), was investigated in node-negative breast cancer patients with small tumors (T1, NO). The 219 stage I patients originated from two series and were diagnosed either from 1978 to 1981 or from 1981 to 1985. The tumors were analyzed for estrogen receptors (ERs) by isoelectric focusing and for cellular DNA content by static cytofluorometry or flow cytometry. RESULTS: A high SPF correlated with the absence of ERs and abnormal DNA content, and was less often found in tumors smaller than 11 mm compared with those with a diameter between 11 and 20 mm. Among the variables age, tumor size, DNA ploidy, ER status, and SPF, only SPF showed a significant association with distant recurrence and breast cancer survival in systemically untreated patients. The relative recurrence rate for patients with an SPF of 10% or greater was three times that for patients with lower SPFs. Estimated 8-year breast cancer survival rates for the same groups were 72% and 91%, respectively. CONCLUSION: This study suggests that cytometric SPF has prognostic significance in stage I breast carcinoma.

The relationship between hormone receptor content and the effect of adjuvant tamoxifen in operable breast cancer.

The relationship between hormone receptor status and the effect of adjuvant tamoxifen in early breast cancer remains controversial. This article presents the results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy in postmenopausal patients. During 1976 to 1984, 1,407 patients were included in the study. Of these, 427 (30%) had high-risk tumors (pN + or pT greater than 30 mm) and were included in a concurrent randomized comparison of postoperative radiotherapy versus adjuvant polychemotherapy. The mean follow-up time was 61/2 years. Tamoxifen improved the recurrence-free survival (RFS) (P less than .01), but the overall survival difference in favor of the tamoxifen-allocated patients was not significant. Data on estrogen (ER) and progesterone receptor (PgR) content were available in 750 patients. Their mean follow-up time was 41/2 years. The effect of tamoxifen was significantly related to ER level (P less than .01). No benefit with tamoxifen was observed among ER-negative patients. The relation to PgR level was of borderline significance (P = .06). Multivariate analysis indicated that most of the interaction between treatment and receptor content was explained by the interaction with ER (P less than .01). The PgR status appeared to modify the effect of tamoxifen among the ER-positive patients and the greatest effect was observed among patients who were positive for both receptors. However, the additional predictive information provided by the PgR assay did not help to identify an unresponsive subgroup of patients.

Proliferative activity of myocardial capillary wall cells in dipyridamole--treated rats.

The hearts of rats treated with dipyridamole were studied by light microscope autoradiography and measurement of tissue radioactivity after intravenous injection of 3H-thymidine. Total tissue radioactivity was significantly increased in the hearts of the dipyridamole-treated animals. Only capillary wall cells were labelled in the autoradiograms. The observations indicate a proliferation of capillary wall cells, suggesting a neoformation of myocardial capillaries during dipyridamole treatment.