Characterization of breast cancer subtypes by quantitative assessment of biological parameters: relationship with clinicopathological characteristics, biological features and prognosis

Objectives

Gene expression analysis has identified several breast cancer subtypes, including luminal, epidermal growth factor receptor-2 positive (HER2+), and basal-like. To determine if our proposed molecular taxonomy correlates with biological and clinical behavior. This is based on four biological markers: estrogen and progesterone receptors (ER and PR, respectively), HER2 and the epidermal growth factor receptor-1 (HER1), all of them being determined by quantitative assays.

Study design

The biological parameters were examined by enzyme immunoassay, radioligand-binding assay or ELISA, in tumors from 787 patients with invasive breast cancer. Patients were prospectively evaluated over a median follow-up period of 50 months. Subtype definitions were as follows: luminal (ER+), HER2+ (HER2+, ER−, PgR−) and basal-like (HER2−, ER−, PgR−). In addition, we divided basal tumors into two groups based on their HER1 status.

Results

A 55.8% of tumors were of luminal type, 11.9% basal-like HER1+, 10.7 basal-like HER1−, and the remainder 21.6% HER2+. Both HER2+ and basal-like subtypes were more frequent in younger and premenopausal women, showing a higher percentage of cases of poorly differentiated tumors and higher S-phase fraction, when compared with those of luminal subtype. Multivariate analysis demonstrated that the subtype of tumor was related to both relapse and overall survival, being those of luminal subtype associated with the best prognosis.

Conclusions

Through the classification of breast tumors in four groups, according to their ER, PgR, HER2 and HER1 status, it is possible to obtain a major division of breast tumors associated with significant differences in biological features and clinical behavior.     

Ultrasonographic and doppler velocimetric evaluation of the levator ani muscle according to the hormonal status

Objective

We aimed to study the cross-sectional area of levator ani muscle and the doppler velocimetric parameters of vessels its in premenopausal and postmenopausal women.

Study design

Sixty-four patients, divided into 3 groups, were assessed: group I (20 women—average age 28 years) premenopausal and nulliparous (control); group II (24 women—average age 38 years, vaginal delivery 1–4) premenopausal with vaginal deliveries; group III (20 women—average age 55 years, parity 0–4) postmenopausal without hormonal therapy. Doppler velocimetry of levator ani muscle vessels through resistance and pulsatility indices was used and the means of the groups compared by adjusting the weighed variance model with multiple comparisons, according to Tukey's method. Similarly, we measured the cross-sectional area of the muscle using ultrasonography.

Results

There was a significant increase in resistance and pulsatility indices in postmenopausal patients as compared to the other two groups. We also observed a significant decrease in the cross-sectional area of the muscle of postmenopausal patients when compared to those in premenopausal.

Conclusion

The obtained results allow us to conclude that levator ani muscle vascularization significantly decreases after menopause (age and/or hipoestrogenism) and that it can be assumed that vaginal delivery does not promote long-term alterations in levator ani muscle vascularization. We also observed a significant decrease in the cross-sectional area of the muscle in postmenopausal women when compared to those in premenopausal.     

The role of high-risk HPV-DNA testing in the male sexual partners of women with HPV-induced lesions

OBJECTIVES: The objectives were to assess the prevalence of high-risk HPV in the male sexual partners of women with HPV-induced lesions, and correlate it with biopsies guided by peniscopy. STUDY DESIGN: Fifty-four asymptomatic male sexual partners of women with low-grade squamous intra-epithelial lesions (LSIL) associated with high-risk HPV were examined between April 2003 and June 2005. The DNA-HPV was tested using a second-generation hybrid capture technique in scraped penile samples. Peniscopy identified acetowhite lesions leading to biopsy. RESULTS: High-risk HPV was present in 25.9% (14 out of 54) of the cases. Peniscopy led to 13 biopsies (24.07%), which resulted in two cases of condyloma, two cases of intra-epithelial neoplasia (PIN) I, one case of PIN II, and eight cases of normal tissue. The high-risk HPV test demonstrated 80% sensitivity, 100% specificity, 100% positive predictive value, and 88.9% negative predictive value for the identification of penile lesions. There was a greater chance of finding HPV lesions in the biopsy in the positive cases of high-risk HPV with abnormal peniscopy (p=0.007); OR=51 (CI 1.7-1527.1). CONCLUSION: Among asymptomatic male sexual partners of women with low-grade intra-epithelial squamous lesions, those infected by high-risk HPV have a higher chance of having abnormal penile tissue compared with male partners without that infection.     

Carcinoma microinvasor de cérvix. El manejo de una neoplasia de buen pronóstico

Introduction

Microinvasive carcinoma represents a subgroup within cervical cancer that is characterized by having a good prognosis and the possibility of treatment through conservative approaches.

Material and methods

We studied data from 60 patients treated at our hospital from 1994 to 2001. The diagnosis was made by the loop electrosurgical excision procedure (LEEP).

Results

Of all treated patients, 83.3% had stage IA1 carcinomas and 16.6% were in stage IA2. All tumors were squamous carcinomas, except one, which was a mucinous adenocarcinoma. Forty patients with stage IA1 tumors underwent total hysterectomy, whilst the remainder were treated by LEEP or, in two patients, through a cervical stump excision. Except for one patient with contraindications for surgery, all IA2 patients underwent radical surgery consisting of radical hysterectomy with bilateral iliac lymphadenectomy. Relapse occurred in only one patient with a stage IA1 tumor, who then underwent colpectomy.

Conclusions

Our data support the current trend of increasing the use of conservative treatments and confirm the excellent prognosis of this neoplasm.     

Study on the prevalence of human papillomavirus in the anal canal of women with cervical intraepithelial neoplasia grade III

Objective

The objective was to evaluate the prevalence of human papillomavirus (HPV) in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade III.

Study design

Two groups were compared. In group I (study group), 40 women who had undergone cervical biopsy with a histopathological result indicating CIN III were evaluated. Group II (control) consisted of 40 women with normal results from colposcopic examination and colpocytological tests. The women in group I who presented high-grade neoplasia in colpocytological tests underwent collection of material from the uterine cervix and anal canal for investigating HPV DNA using the Hybrid Capture II^® technique. Colposcopy and cervical biopsy were then performed. If CIN III was confirmed, HPV DNA was investigated in the material collected. In group II, colpocytological tests and colposcopy were performed and, if normal, the procedure was similar to that followed for group I, except that no biopsy was performed.

Results

In group I, 39 women (97.5%) were positive for HPV in the uterine cervix and 14 women (35%) in the anal canal. In group II, only four women (10%) had a positive HPV test, for both the uterine cervix and the anal canal.

Conclusions

The prevalence of HPV in the anal canal of the women with CIN III was greater than in the women without CIN III.     

17alpha-hydroxy-progesterone effects on cervical proinflammatory agents in women at risk for preterm delivery

We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate (17P) on cervical ripening is mediated by cervical proinflammatory agents. Women with singleton pregnancy and intact membranes, between 25 and 33 weeks + 6 days, were randomly allocated either to observation (22 cases, controls) or to receive 341 mg of intramuscular 17P (23 cases, 17P group), twice a week, until 36 weeks. Just before randomization, 7 and 21 days later, a cervical swab for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and nitrates/nitrites (NOx) assays was collected. Moreover, an ultrasound measure of cervical length (CL) was performed at the same time. At randomization, both groups of women showed similar levels of cervical ILs and NOx. In the 17P group, cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036); in controls, they remained stable throughout the observation period. There was no significant change in IL-6, IL-8, TNF-alpha, and NOx in either group. Women in the control group had a progressive CL shortening until day 21 (median shortening of 4 mm), and this shortening was significantly less in the 17P group (median shortening of 2 mm; P = 0.017). In patients at risk of preterm labor, high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix.     

Partial placenta increta and methotrexate therapy: three case reports

The term placenta accreta is used to describe any placental implantation in which there is abnormally firm adherence to the uterine wall. This condition complicates 1/2,500 deliveries and is rising in incidence. Abnormal placentation is associated with increased maternal morbidity and mortality from severe hemorrhage, uterine perforation, infection and loss of fertility. The reported experience of methotrexate treatment in the conservative management of placenta accreta is scant. Three cases of partial placenta increta managed with methotrexate are described. The patients were assessed with clinical surveillance, serum beta human chorionic gonadotrophin (beta-hCG) and imaging (ultrasonography and magnetic resonance in one case). In all cases conservative management with methotrexate resulted in undetectable serum beta-hCG, a decrease in the size of partial placenta retained, and undetectable vascularization.