Mammographic features of benign breast lesions and risk of subsequent breast cancer in women attending breast cancer screening.

OBJECTIVES: To evaluate the mammographic features in women with benign breast disease (BBD) and the risk of subsequent breast cancer according to their mammographic findings. METHODS: We analyzed data from a Spanish cohort of women screened from 1995 to 2015 and followed up until December 2017 (median follow-up, 5.9 years). We included 10,650 women who had both histologically confirmed BBD and mammographic findings. We evaluated proliferative and nonproliferative BBD subtypes, and their mammographic features: architectural distortion, asymmetries, calcifications, masses, and multiple findings. The adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for breast cancer were estimated using a Cox proportional hazards model. We plotted the adjusted cumulative incidence curves. RESULTS: Calcifications were more frequent in proliferative disease with atypia (43.9%) than without atypia (36.8%) or nonproliferative disease (22.2%; p value < 0.05). Masses were more frequent in nonproliferative lesions (59.1%) than in proliferative lesions without atypia (35.1%) or with atypia (30.0%; p value < 0.05). Multiple findings and architectural distortion were more likely in proliferative disease (16.1% and 4.7%) than in nonproliferative disease (12.8% and 1.9%). Subsequent breast cancer occurred in 268 (2.5%) women. Compared with women who had masses, the highest risk of subsequent breast cancer was found in those with architectural distortions (aHR, 2.21; 95% CI, 1.16-4.22), followed by those with multiple findings (aHR, 1.89; 95% CI, 1.34-2.66), asymmetries (aHR, 1.66; 95% CI, 0.84-3.28), and calcifications (aHR, 1.60; 95% CI, 1.21-2.12). CONCLUSION: BBD subtypes showed distinct mammographic findings. The risk of subsequent breast cancer was high in those who have shown architectural distortion, multiple findings, asymmetries, and calcifications than in women with masses. KEY POINTS: • The presence of mammographic findings in women attending breast cancer screening helps clinicians to assess women with benign breast disease (BBD). • Calcifications were frequent in BBDs with atypia, which are the ones with a high breast cancer risk, while masses were common in low-risk BBDs. • The excess risk of subsequent breast cancer in women with BBD was higher in those who showed architectural distortion compared to those with masses.

Risk of Breast Cancer in Women with False-Positive Results according to Mammographic Features.

Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article.

p53 expression in breast cancer predicts tumors with low probability of non-sentinel nodes infiltration.

AIM: Several predictive tools of non-sentinel lymph nodes neoplastic involvement when a positive sentinel lymph node is found have been described. However, molecular factors have been rarely evaluated to build these tools. The aim of this study was to establish which factors predicted non-sentinel lymph nodes infiltration in our setting, including some molecular factors. MATERIAL AND METHODS: We carried out a retrospective review of 161 patients with breast cancer and a positive sentinel lymph node who had undergone axillary lymph node dissection, none of whom had received neoadjuvant treatment. Features evaluated as predictive factors for non-sentinel node positivity were: menopausal status, tumor size, histological subtype, histological grade, lymphovascular invasion, extracapsular invasion, Ki67 index, hormonal receptors, CerbB2 and p53 expression, size of sentinel lymph node metastases and number of sentinel lymph nodes affected. RESULTS: Tumor size (P = 0.001), size of sentinel lymph node metastases (P = 0.001), lobular invasive carcinoma (P = 0.05) and lymphovascular invasion (P = 0.006) were significantly associated with non-sentinel lymph node positivity. Tumor p53 positive expression was strongly associated with non-sentinel lymph node negativity (P = 0.000). In multivariate analysis, all these factors but tumor size maintained their significance. The discrimination power of the model calculated by the area under the receiver-operator curve was 0.811 (95% confidence interval, 0.741-0.880). CONCLUSION: p53 expression in breast cancer was highly predictive of non-sentinel lymph node negativity in our study. New studies should evaluate if it would be useful to add p53 expression to other existing predictive tools.

P53 expression correlates with low axillary tumor burden in breast cancer.

BACKGROUND: The p53 mutation in breast cancer confers a worse prognosis and is usually associated with p53 overexpression (p53+) on immunohistochemistry. Previous studies have shown that p53+ tumors could be associated with low axillary tumor burden (ATB). OBJECTIVE: We aimed to evaluate the association between p53+ and ATB in a large series of breast cancers as an aid to personalizing axillary surgical treatment. METHODS: We retrieved 1762 infiltrating breast carcinomas from our database that were treated with upfront surgery in Hospital del Mar from 2004 to 2018. We compared p53+ and p53-negative (p53-) tumors in terms of the percentage of cases with high ATB and overall survival. This comparison was made overall and for each immunophenotype. RESULTS: Overall, 18.7% of breast tumors were p53+. High ATB was less common in p53+ tumors than in p53- tumors in the luminal B-Her2-negative immunophenotype (6.2% versus 16.9%, respectively, P = 0.025), but not in the other immunophenotypes or overall. Overall survival was worse in patients with p53+ breast cancer (P = 0.002). CONCLUSION: p53+ breast cancers were associated with worse overall survival. However, low ATB was more common in these tumors than in p53- tumors in the luminal B-Her2-negative subtype. Information on p53 expression could be of use to predict ATB in some breast cancer tumors.

Validation of the Spanish electronic version of the BREAST-Q questionnaire.

BACKGROUND: Patient-reported outcome measures (PROMs) have gained considerable interest in health care moving beyond traditional outcome measures of morbidity and mortality. In breast cancer surgery, women's' perceptions of appearance, function and quality of life have become increasingly important. The BREAST-Q questionnaire is a validated PROM for use in cosmetic and reconstructive breast surgery in clinical practice. The objective of this study was to validate the Spanish electronic version of the BREAST-Q questionnaire, to verify the measurement equivalence of digital and paper versions and to identify the possible disadvantages and advantages of implementing this new tool. METHODS: The study population included 113 patients undergoing breast cancer survey at a single hospital in Barcelona (Spain) who were able to complete both the electronic and paper versions of the preoperative module of the BREAST-Q questionnaire. RESULTS: The intraclass correlation coefficient (ICC) in the four domains of the questionnaire between the two versions of the questionnaire was >0.9, with a weighted kappa of >0.74 at item level. The reliability of the internal consistency was also excellent, with Cronbach's alpha coefficient of >0.70 in all domains. Age was a limiting factor for the delivery of the electronic version of BREAST-Q, with 69 years of age as the cut-off point to obtain reliable results. CONCLUSIONS: The interchangeability of the electronic and paper versions of the BREAST-Q questionnaire facilitates implementation of this instrument in routine surgical oncological practice.

Accuracy of sentinel node mapping in patients with biopsy-proven metastatic axillary lymph nodes and upfront surgery: preliminary results of the Multimodal Targeted Axillary Surgery (MUTAS) trial.

Background: Some studies suggested that the patients included in the Z0011 trial may represent patients with ultrasound-negative axillary nodes and axillary invasion diagnosed by sentinel node (SN) biopsy. Nevertheless, the National Comprehensive Cancer Network (NCCN) guidelines recommend SN mapping if 1 or 2 suspicious lymph nodes are identified on axillary ultrasound (AU). The aim of this preliminary phase of the Multimodal Targeted Axillary Surgery (MUTAS) trial was to establish the accuracy of SN mapping in patients with axillary involvement undergoing upfront surgery. Methods: Between September 2019 and March 2022, we recruited patients with biopsy-proven metastatic axillary nodes and upfront surgery from a single center. We performed SN mapping in these patients before the surgical intervention, which included axillary lymph node dissection. The biopsy-proven metastatic node, SNs and the remaining axillary nodes were excised separately. SN status was considered representative of the status of the remaining axillary nodes. We calculated the sensitivity, specificity, negative predictive value and positive predictive value of the SN, overall and in patients with palpable nodes, in those with non-palpable nodes and an AU leading to diagnosis of axillary involvement, in those with 1 or 2 suspicious nodes on AU, and in patients with a single suspicious node on AU. We evaluated clinical, imaging and pathology features as predictors of the status of the remaining axillary nodes, false-negatives, and false-positives. Results: We included 25 patients in this phase. The false-negative rate of SN mapping was 28% overall, 21.42% for patients with palpable nodes, 36.36% for patients with non-palpable nodes and an AU diagnosis of axillary involvement, 28.75% for those with 1 or 2 suspicious nodes on AU, and 15.38% in patients with a single suspicious node on AU. The negative predictive value was highest in patients with a single suspicious node on AU (75%). The only significant predictive factor was that FN showed a higher Ki67 index score. Conclusions: In this study, SN mapping was not reliable in patients with biopsy-proven metastatic axillary nodes and upfront surgery for any of the subgroups studied. Further research should elucidate the best staging pathways in these patients to avoid premature de-escalation.

Assessing variability in breast cancer management across the world: results of a questionnaire survey amongst global international experts in breast cancer management.

Background: Breast cancer is the most common cancer in women worldwide with an estimated 2.3 million breast cancer cases diagnosed annually. The outcome of breast cancer management varies widely across the globe which could be due to a multitude of factors. Hence, a blanket approach in standardisation of care across the world is neither practical nor feasible. Aim: To assess the extent and type of variability in breast cancer management across the globe and to do a gap analysis of patient care pathway. Method: An online questionnaire survey and virtual consensus meeting was carried out amongst 31 experts from 25 countries in the field of breast cancer surgical management. The questionnaire was designed to understand the variability in diagnosis and treatment of breast cancer, and potential factors contributing to this heterogeneity. Result: The questionnaire survey shows a wide variation in breast surgical training, diagnosis and treatment pathways for breast cancer patients. There are several factors such as socioeconomic status, patient culture and preferences, lack of national screening programmes and training, and paucity of resources, which are barriers to the consistent delivery of high-quality care in different parts of the world. Conclusion: On-line survey platforms distributed to global experts in breast cancer care can assess gaps in the diagnosis and treatment of breast cancer patients. This survey confirms the need for an in-depth gap analysis of patient care pathways and treatments to enable the development of personalised plans and policies to standardise high quality care.

Factors affecting surgical margins in nonpalpable breast tumors excised with the radioguided occult lesion localization approach.

AIM: Most breast surgeons generally assume that obtaining negative margins in nonpalpable tumors is a matter of concern. The aim of this study was to examine whether it is easier to obtain negative margins in palpable tumors than in nonpalpable tumors excised with the radioguided occult lesion localization (ROLL) technique. METHODS: A retrospective review was made of nonpalpable breast cancers excised with the ROLL technique (ROLL group, n = 83) and palpable breast cancers in which breast conservative therapy was performed (Palpable group, n = 77). The margin status and the size of the minimum margin obtained when it was negative were reviewed. RESULTS: The percentage of resections with negative margins was similar in both groups: 51.9% in the Palpable group and 61.4% in the ROLL group. There was no difference between the two groups in the minimum margin obtained: mean ± SD, 5.53 ± 3.146 mm in the Palpable group and 5.96 ± 3.039 mm in the ROLL group. Risk factors for failing to obtain negative margins were analyzed in both groups and were similar. These risk factors included histological grade, extensive intraductal carcinoma and c-erbB2 status. CONCLUSION: It is concluded that excision of nonpalpable breast tumors with the ROLL approach obtains similar results for margins as conservative surgery performed for palpable tumors.

Developing and validating an individualized breast cancer risk prediction model for women attending breast cancer screening.

BACKGROUND: Several studies have proposed personalized strategies based on women's individual breast cancer risk to improve the effectiveness of breast cancer screening. We designed and internally validated an individualized risk prediction model for women eligible for mammography screening. METHODS: Retrospective cohort study of 121,969 women aged 50 to 69 years, screened at the long-standing population-based screening program in Spain between 1995 and 2015 and followed up until 2017. We used partly conditional Cox proportional hazards regression to estimate the adjusted hazard ratios (aHR) and individual risks for age, family history of breast cancer, previous benign breast disease, and previous mammographic features. We internally validated our model with the expected-to-observed ratio and the area under the receiver operating characteristic curve. RESULTS: During a mean follow-up of 7.5 years, 2,058 women were diagnosed with breast cancer. All three risk factors were strongly associated with breast cancer risk, with the highest risk being found among women with family history of breast cancer (aHR: 1.67), a proliferative benign breast disease (aHR: 3.02) and previous calcifications (aHR: 2.52). The model was well calibrated overall (expected-to-observed ratio ranging from 0.99 at 2 years to 1.02 at 20 years) but slightly overestimated the risk in women with proliferative benign breast disease. The area under the receiver operating characteristic curve ranged from 58.7% to 64.7%, depending of the time horizon selected. CONCLUSIONS: We developed a risk prediction model to estimate the short- and long-term risk of breast cancer in women eligible for mammography screening using information routinely reported at screening participation. The model could help to guiding individualized screening strategies aimed at improving the risk-benefit balance of mammography screening programs.

Risk of breast cancer two years after a benign biopsy depends on the mammographic feature prompting recall.

OBJECTIVE: We aimed to explore whether the type of mammographic feature prompting a false-positive recall (FPR) during mammography screening influences the risk and timing of breast cancer diagnosis, particularly if assessed with invasive procedures. STUDY DESIGN: We included information on women screened and recalled for further assessment in Spain between 1994 and 2015, with follow-up until 2017, categorizing FPRs by the assessment (noninvasive or invasive) and mammographic feature prompting the recall. MAIN OUTCOME MEASURES: Breast cancer rates in the first two years after FPR (first period) and after two years (second period). RESULTS: The study included 99,825 women with FPRs. In both periods, the breast cancer rate was higher in the invasive assessment group than in the noninvasive group (first period 12 ‰ vs 1.9 ‰, p < 0.001; second period 4.4‰ vs 3.1‰, p < 0.001). During the first period, the invasive assessment group showed diverse breast cancer rates for each type of mammographic feature, with a higher rate for asymmetric density (31.9‰). When the second period was compared with the first, the breast cancer rate decreased in the invasive assessment group (from 12‰ to 4.4‰, p < 0.001) and increased in the noninvasive assessment group (from 1.9‰ to 3.1‰, p < 0.001). CONCLUSION: In the context of mammography screening, the risk of breast cancer diagnosis during the first two years after FPR was particularly high for women undergoing invasive assessment; importantly, the risk was modified by type of mammographic feature prompting the recall. This information could help to individualize follow-up after exclusion of malignancy.

Readmissions and complications in breast ductal carcinoma in situ: A retrospective study comparing screen- and non-screen-detected patients.

OBJECTIVE: Population-wide mammographic screening programs aim to reduce breast cancer mortality. However, a broad view of the harms and benefits of these programs is necessary to favor informed decisions, especially in the earliest stages of the disease. Here, we compare the outcomes of patients diagnosed with breast ductal carcinoma in situ in participants and non-participants of a population-based mammographic screening program. METHODS: A retrospective cohort study of all patients diagnosed with breast ductal carcinoma in situ between 2000 and 2010 within a single hospital. A total of 211 patients were included, and the median follow-up was 8.4 years. The effect of detection mode (screen-detected and non-screen-detected) on breast cancer recurrences, readmissions, and complications was evaluated through multivariate logistic regression analysis. RESULTS: In the majority of women, breast ductal carcinoma in situ was screen-detected (63.5%). Screen-detected breast ductal carcinoma in situ was smaller in size compared to those non-screen-detected (57.53% < 20 mm versus 78.03%, p = 0.002). Overall, breast-conserving surgery was the most frequent surgery (86.26%); however, mastectomy was higher in non-screen-detected breast ductal carcinoma in situ (20.78% versus 9.7%, p = 0.024). Readmissions for mastectomy were more frequent in non-screen-detected breast ductal carcinoma in situ. Psychological complications, such as fatigue, anxiety, and depression, had a prevalence of 15% within our cohort. Risk of readmissions and complications was higher within the non-screen-detected group, as evidenced by an odds ratio = 6.25 (95% confidence interval = 1.95-19.99) for readmissions and an odds ratio = 2.41 (95% confidence interval = 1.95-4.86) for complications. CONCLUSIONS: Our findings indicate that women with breast ductal carcinoma in situ breast cancer diagnosed through population-based breast cancer screening program experience a lower risk of readmissions and complications than those diagnosed outside these programs. These findings can help aid women and health professionals make informed decisions regarding screening.

Coordinated signals from PARP-1 and PARP-2 are required to establish a proper T cell immune response to breast tumors in mice.

Poly(ADP-ribose)-polymerase (PARP)-1 and PARP-2 play an essential role in the DNA damage response. Based on this effect of PARP in the tumor cell itself, PARP inhibitors have emerged as new therapeutic tools both approved and in clinical trials. However, the interactome of multiple other cell types, particularly T cells, within the tumor microenvironment are known to either favor or limit tumorigenesis. Here, we bypassed the embryonic lethality of dually PARP-1/PARP-2-deficient mice by using a PARP-1-deficient mouse with a Cd4-promoter-driven deletion of PARP-2 in T cells to investigate the understudied role of these PARPs in the modulation of T cell responses against AT-3-induced breast tumors. We found that dual PARP-1/PARP-2-deficiency in T cells promotes tumor growth while single deficiency of each protein limited tumor progression. Analysis of tumor-infiltrating cells in dual PARP-1/PARP-2-deficiency host-mice revealed a global change in immunological profile and impaired recruitment and activation of T cells. Conversely, single PARP-1 and PARP-2-deficiency tends to produce an environment with an active and partially upregulated immune response. Our findings pinpoint opposite effects of single and dual PARP-1 and PARP-2-deficiency in modulating the antitumor response with an impact on tumor progression, and will have implications for the development of more selective PARP-centered therapies.

Mammographic extent of microcalcifications and oestrogen receptor expression affect preoperative breast carcinoma in situ size estimation.

BACKGROUND: The aim of our study was to establish which clinical, radiologic and pathologic factors could predict the risk of under- and overestimation of the breast ductal carcinoma in situ (DCIS) size when preoperatively measuring the maximum mammographic extent of microcalcifications (MEM). METHODS: We made a retrospective review of patients with a DCIS treated in our Breast Unit between May 2005 and May 2012. Clinical, pathologic and radiologic data were evaluated as possible predictive factors for over- or underestimation of DCIS size when measuring MEM. RESULTS: We obtained precise measurements of MEM in 82 patients (84 DCIS lesions). Maximum MEM measurement correctly estimated maximum pathology size in 57 lesions (68.7 %). Patients with a correctly estimated DCIS, with an underestimated DCIS and with an overestimated DCIS significantly differed in DCIS ER expression (p = 0.022) and in maximum MEM measurement (p = 0.000). Constructing two ROC curves, we found that a maximum MEM measurement ≥25 mm and ER expression ≥90 % were both discrimination points for overestimation and ER ≤ 45 % was a discrimination point for underestimation. Using these cutoff points, we defined four groups of patients with different risks of over- and underestimation. CONCLUSIONS: Risk of over- or underestimation of DCIS size through MEM measurement depends on DCIS ER expression and MEM itself. Identifying which patients are at a significant risk of over- or underestimation could help the breast surgeon when discussing the surgical options with the patient.

Biomarkers expression in benign breast diseases and risk of subsequent breast cancer: a case-control study.

Women with benign breast diseases (BBD) have a high risk of breast cancer. However, no biomarkers have been clearly established to predict cancer in these women. Our aim was to explore whether estrogen receptor (ER), progesterone receptor (PR), and Ki67 expression stratify risk of breast cancer in screened women with BBD. We conducted a nested case-control study. Women with breast cancer and prior BBDs (86 cases) were matched to women with prior BBDs who were free from breast cancer (172 controls). The matching factors were age at BBD diagnosis, type of BBD, and follow-up time since BBD diagnosis. ER, PR, and Ki67 expression were obtained from BBDs' specimens. Conditional logistic regression was used to estimate odds ratios (ORs), and 95% confidence intervals (CIs) of breast cancer risk according to ER, PR, and Ki67 expression. Women with >90% of ER expression had a higher risk of breast cancer (OR = 2.63; 95% CI: 1.26-5.51) than women with ≤70% of ER expression. Similarly, women with >80% of PR expression had a higher risk of breast cancer (OR = 2.22; 95% CI: 1.15-4.27) than women with ≤40% of PR expression. Women with proliferative disease and ≥1% of Ki67 expression had a nonsignificantly increased risk of breast cancer (OR = 1.16; 95% CI: 0.46-2.90) than women with <1% of Ki67 expression. A high expression of ER and PR in BBD is associated with an increased risk of subsequent breast cancer. In proliferative disease, high Ki67 expression may also have an increased risk. This information is helpful to better characterize BBD and is one more step toward personalizing the clinical management of these women.

Human papillomavirus and breast cancer: no evidence of association in a Spanish set of cases.

BACKGROUND/AIM: Great controversy exists about the association between Human Papillomavirus (HPV) and breast tumors. The aim of this study was to explore the presence of HPV DNA in a large set of breast cancer cases. MATERIALS AND METHODS: Techniques used followed the standards for an international retrospective survey of HPV-DNA genotyping, coordinated by our own group and the DDL Laboratories in Rijswijk, the Netherlands. Paraffin-embedded samples were used. SPF-10 broad-spectrum primers were applied, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse-line probe assay. RESULTS: A total of 78 samples were included in the study, 2 of benign conditions and 76 carcinomas, including different histological subtypes. HPV was not present in any of the specimens studied irrespective of histology, hormonal status and stage of disease. CONCLUSION: Our data do not support the involvement of HPV in breast carcinogenesis as no evidence of its presence was found.

The endometria of patients with endometriosis show higher expression of class I human leukocyte antigen than the endometria of healthy women.

OBJECTIVE: To compare the expression of class I human leukocyte antigen (HLA I) in endometrial samples from patients with and without endometriosis. DESIGN: Cross-sectional study. SETTING: Acute-care teaching hospital in Barcelona, Spain. PATIENT(S): The endometriosis group included 32 patients for whom the only diagnosis during an operation was endometriosis. The control group included 20 women who underwent a laparoscopy and in whom no evidence of endometriosis or any other genital disease was seen. INTERVENTION(S): Samples of endometrium were obtained by curettage and immediately frozen. A pan-HLA I mouse antihuman IgG2a monoclonal antibody was used for immunohistochemical study. MAIN OUTCOME MEASURE(S): Frequency of positive glandular and stromal cells was evaluated in each section. RESULT(S): A significantly higher expression of HLA I in the endometriosis group than in controls, both in the glandular cells (median 100% vs. 80%) and in the stromal cells (median 60% vs. 20%), was observed. CONCLUSION(S): Patients with endometriosis had a significantly higher expression of HLA I molecules in endometrial cells than did the controls. This could be a possible explanation for their higher resistance to natural killer cytolysis.

The depolarized expression of the alpha-6 integrin subunit in the endometria of women with endometriosis.

OBJECTIVE: The current study sought to compare the endometrial localization of the integrin subunit alpha-6 in women with endometriosis and women without the disease. Alpha-6 integrins have an important function, not only in the attachment of cells to the extracellular matrix and laminin, but they also serve as inductors of cell migration and invasion, depending on their pattern of expression in the cell membrane. METHODS: The endometriosis group consisted of 32 women with a confirmed diagnosis of endometriosis by laparoscopy or laparotomy. The control group consisted of 20 women not having endometriosis or any other gynecologic disease at laparoscopy. Endometria were obtained by biopsy. Immunohistochemical techniques were used to assess alpha-6 localization. In each section, the percentage of positive cells and the localization of expression were evaluated. RESULTS: All glandular cells expressed alpha-6 in all of the samples but presented two different patterns, either only in the basal side of the cells (polarized) or also in other sides of the cells (depolarized). The percentage of samples showing depolarized expression was significantly higher in the endometriosis group (66.6% vs 15.8%, chi2 =12.09, P = .001). CONCLUSIONS: The endometria of women with endometriosis more frequently show a depolarized expression of integrin subunit alpha-6, a characteristic usually found in highly proliferating cells with migrating and invasive abilities.