Pathological macroscopic evaluation of breast density versus mammographic breast density in breast cancer conserving surgery.

Correlation between imaging and anatomopathological breast density has been superficially explored and is heterogeneous in current medical literature. It is possible that mammographic and pathological findings are divergent. The aim of this study is to evaluate the association between breast density classified by mammography and breast density of pathological macroscopic examination in specimens of breast cancer conservative surgeries. Post-hoc, exploratory analysis of a prospective randomized clinical trial of patients with breast cancer candidates for breast conservative surgery. Breast mammographic density (MD) was analyzed according to ACR BI-RADS® criteria, and pathologic macroscopic evaluation of breast density (PMBD) was estimated by visually calculating the ratio between stromal and fatty tissue. From 412 patients, MD was A in 291 (70,6%), B in 80 (19,4%) B, C in 35 (8,5%), and D in 6 (1,5%). Ninety-nine percent (201/203) of patients classified as A+B in MD were correspondently classified in PMBD. Conversely, only 18.7% (39/209) of patients with MD C+D were classified correspondently in PMBD (p < 0.001). Binary logistic regression showed age (OR 1.06, 1.01-1.12 95% CI, p 0.013) and nulliparity (OR 0.39, 0.17-0.96 95% CI, p 0.039) as predictors of A+B PMBD. Conclusion: Mammographic and pathologic macroscopic breast density showed no association in our study for breast C or D in breast image. The fatty breast was associated with older patients and the nulliparity decreases the chance of fatty breasts nearby 60%.

Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status.

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.

Validation of the Residual Cancer Burden Index as a prognostic tool in women with locally advanced breast cancer treated with neoadjuvant chemotherapy.

AIMS: To correlate the 'Residual Cancer Burden' (RCB) index with overall survival (OS) and disease-free survival (DFS) in women undergoing neoadjuvant chemotherapy at the Cancer Institute of the State of São Paulo. METHODS: We analysed the medical records of patients with breast cancer who underwent neoadjuvant chemotherapy and breast surgery, from 2011 to December 2017. Variables analysed were age, clinical and pathological staging, molecular subtype, number of recurrences or metastases, number of deaths, value and class of the RCB index. We used the Kaplan-Meier and the log-rank statistics to evaluate the possible association between RCB and OS and DFS. A regression model was used to determine the independent association of the RCB with the outcomes controlling for confounding factors. RESULTS: 347 patients were included in the analysis with a mean age of 49.39 years. Initial clinical staging was T3 in 57.9% of patients and 43.8% of patients had N1 axillary status. Survival analysis showed a statistically significant better prognosis for the RCB 0 (pCR) subgroup compared with RCB 1, 2 and 3 (log rank p=0.01). In a multivariate analysis, only the RCB classification showed a statistically significant correlation with DFS (RCB 1, HR 6.9, CI 1.9 to 25.4, p=0.004; RCB 2, HR 4.2, CI 1.6 to 10.8, p=0.03; and RCB 3, HR 7.6, CI 2.76 to 20.8, p=0.00). CONCLUSION: We demonstrated a positive and significant relationship between the RCB index and the risk of relapse and death.

Microablative fractional radiofrequency as a therapeutic option for vulvar lichen sclerosus: a pilot study.

OBJECTIVES: To assess the clinical response to and the histomorphometric effects of microablative fractional radiofrequency (MFR) in women with symptomatic vulvar lichen sclerosus (VLS). METHODS: This was a pilot study on the use of MFR for the treatment of VLS. Upon recruitment and at each treatment session, all participants were examined and each of their symptoms were rated on a visual analog scale. After the procedure, the participants completed a satisfaction questionnaire. We compared the morphometric findings of vulvar biopsies performed at enrollment and after the last treatment session. The participants were divided into three groups according to previous treatment with corticosteroids: G1, no previous treatment; G2, treated for up to 5 years; and G3, treated for >5 years. RESULTS: This study included 26 women. After two to three sessions, most participants in all groups became either "asymptomatic" or "much better" than before treatment and were "very satisfied" or "satisfied" with the intervention. Pruritus and burning sensation were the most frequently reported symptoms. Nearly 40% of the participants in all groups reported complete remission of symptoms. The improvement was rated as moderate or higher by 80%, 76%, and 66% of the women in groups 1, 2, and 3, respectively. The improvement of symptoms persisted for 11 months (range, 7-16 months), on average, after the treatment. Type III collagen concentration significantly increased and was associated with important symptom improvement. Tissue trophism and vascularization also increased but did not reach statistical significance, probably because of the small number of cases. CONCLUSIONS: MFR may be an effective and safe treatment for symptomatic VLS.

Microablative fractional radiofrequency as a therapeutic option for vulvar lichen sclerosus: a pilot study

OBJECTIVES: To assess the clinical response to and the histomorphometric effects of microablative fractional radiofrequency (MFR) in women with symptomatic vulvar lichen sclerosus (VLS). METHODS: This was a pilot study on the use of MFR for the treatment of VLS. Upon recruitment and at each treatment session, all participants were examined and each of their symptoms were rated on a visual analog scale. After the procedure, the participants completed a satisfaction questionnaire. We compared the morphometric findings of vulvar biopsies performed at enrollment and after the last treatment session. The participants were divided into three groups according to previous treatment with corticosteroids: G1, no previous treatment; G2, treated for up to 5 years; and G3, treated for >5 years. RESULTS: This study included 26 women. After two to three sessions, most participants in all groups became either "asymptomatic" or "much better" than before treatment and were "very satisfied" or "satisfied" with the intervention. Pruritus and burning sensation were the most frequently reported symptoms. Nearly 40% of the participants in all groups reported complete remission of symptoms. The improvement was rated as moderate or higher by 80%, 76%, and 66% of the women in groups 1, 2, and 3, respectively. The improvement of symptoms persisted for 11 months (range, 7-16 months), on average, after the treatment. Type III collagen concentration significantly increased and was associated with important symptom improvement. Tissue trophism and vascularization also increased but did not reach statistical significance, probably because of the small number of cases. CONCLUSIONS: MFR may be an effective and safe treatment for symptomatic VLS.

Nipple-sparing mastectomy for early breast cancer: the importance of intraoperative evaluation of retroareolar margins and intra-nipple duct removal.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly performed for breast cancer (BC) treatment. To ensure local control with this procedure, it is important to obtain clear surgical margins. Here, we aimed to estimate the confidence in intraoperative evaluation of the retroareolar margin (IERM) and the necessity of removing the intra-nipple ducts. METHODS: In this retrospective cohort study, we evaluated 224 BC (infiltrating carcinoma 178, ductal carcinoma in situ 46) patients, who underwent NSM. IERM was determined via cytology and frozen sections. Following gland removal, the intra-nipple ducts were excised and embedded in paraffin for analysis. The retroareolar tissue was also paraffin-embedded and reanalyzed for definitive evaluation of retroareolar margins (DERM). The IERM predictive capacity in relation to DERM and the frequency of intra-nipple duct involvement were estimated. RESULTS: IERM classified the sub-nipple areolar complex area as cancer-free in 219 cases (97.8%). The condition of clear retroareolar margin was confirmed by DERM in 216 cases (98.6%). The IERM accuracy was estimated as 98.6%. Ductal carcinoma in situ was detected in intra-nipple ducts using paraffin sections in 1.8% of the cases, despite clear IERM (4/219). CONCLUSIONS: In conclusion, IERM affords high accuracy and its results are suitable to manage the nipple-areolar complex. Nevertheless, some patients may retain residual disease in the intra-nipple ducts; thus, these ducts should ideally be removed during NSM.

L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion.

BACKGROUND: Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. MATERIALS AND METHODS: We studied 47 consecutive patients aged 37-88 (61.34±10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. RESULTS: LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. CONCLUSIONS: L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.

PRIMARY BREAST LYMPHOMA PRESENTING AS LOCALLY ADVANCED BREAST CANCER: A CASE REPORT / Linfoma primário apresentando-se como um câncer de mama localmente avançado: relato de caso

Hematopoietic diseases can be found in the breast and mimic a mammary neoplasm, such as leukemia and/or lymphoma. Although lymphomas are considered lymph node tumors, 25-40% have extranodal sites. Primary lymphomas of the breast represent 0.1- 0.5% of all breast neoplasms and may have primary or secondary origin. Primary lymphomas normally start in the breast without involvement of other sites. The diagnosis is made through physical and pathological examination. We report a 77-year-old female who had a locally advanced mass in the right breast associated with inflammatory signs and symptoms and with palpable axillary lymph nodes. The imaging tests were non-specific and didn't help the diagnosis. The pathology report revealed a diffuse, B-cell lymphoma infiltrating the breast (lymphoma non-Hodgkin's). Due to the rarity of the case, and the unknown pathogenesis systemic chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) regime were performed. The use of rituximab, as well as radiotherapy, remain controversial in the literature, but for some authors the radiotherapy is indicated with a total dose of 30 to 45 GY. Our patient performed radiotherapy of the breast and axilla. Because of total remission of the disease, it was not necessary complementary treatment or breast surgery.

Doenças hematopoiéticas podem ser encontradas na mama e simular uma neoplasia mamária, como leucemia e/ou linfoma. Apesar de os linfomas serem considerados tumores linfonodais, 25-40% acometem sítios extranodais, sendo um deles a mama. Os linfomas primários da mama representam 0,1-0,5% de todas as neoplasias da mama. Podem ter origem primária ou secundária. Os primários normalmente iniciam-se na mama sem acometimento de outros sítios linfonodais. O diagnóstico é feito através do exame físico e anatomopatológico. Relatamos um caso de uma paciente, idosa, de 77 anos, que compareceu em nosso serviço com uma massa progressiva envolvendo toda a mama direita, ulcerada e associada a sinais e sintomas inflamatórios com linfonodos axilares palpáveis. Os exames de imagem foram inespecíficos e não ajudaram no diagnóstico, não tendo sido recomendados para o rastreio dessa neoplasia. O exame anatomopatológico revelou um linfoma de células B difuso infiltrando a mama (linfoma não Hodgkin). Devido à raridade do caso, a etiopatogenia é desconhecida, e o tratamento foi realizado com os esquemas quimioterápicos para linfoma segundo o consenso para linfomas de células B, sendo a base o tratamento com antraciclinas. A paciente realizou seis ciclos de CHOP (ciclofosfamida, doxorrubicina, vincristina e prednisona), com a regressão total da lesão. O uso do rituximabe, bem como a radioterapia, permanecem controversos na literatura, mas a radioterapia é indicada por alguns autores na dose de 30 a 45 GY. Nossa paciente realizou radioterapia da mama e da axila com ausência de remissão da doença, não tendo sido necessário tratamento complementar ou cirurgia da mama.

SPECT-CT-Guided Thoracoscopic Biopsy of Sentinel Lymph Nodes in the Internal Mammary Chain in Patients With Breast Cancer: A Pilot Study.

OBJECTIVE: The objective of this study was to determine the impact of the use of single-photon emission computed tomography fused with computed tomography (SPECT-CT) on thoracoscopic biopsy of sentinel lymph nodes (SLNs) in the internal mammary chain in patients with breast cancer by evaluating resultant changes in staging and their clinical implications. METHODS: Between September 2010 and January 2014, we performed lymphoscintigraphy-assisted thoracoscopic biopsy of the internal mammary chain SLN in 20 patients with breast cancer. Single-photon emission computed tomography fused with computed tomography was also used in 13 of these patients. The sentinel nodes were surgically identified with the aid of a gamma probe. RESULTS: Sentinel lymph nodes were identified surgically in 19 of 20 patients. In the 13 patients in whom SPECT-CT was used, it readily identified SLNs, especially when they were located over an intercostal space. Change of staging occurred in three patients (15%), two of whom accordingly received adjuvant radiotherapy to the internal thoracic chain. CONCLUSIONS: Compared with lymphoscintigraphy alone, the use of SPECT-CT improves localization of the SLN in the internal mammary chain, allowing more accurate planning of each individual's treatment.

Advanced small-cell ovarian carcinoma, hypercalcemic type: a challenging therapeutic entity.

Small-cell ovarian carcinoma (SCOC) is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT) can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS) can also occur, jeopardizing the patient's outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.

Malignant paratesticular mesothelioma.

Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor that usually affects patients after the sixth decade of life. Exposure to asbestos is a known risk factor. Enlargement of the scrotal volume is the most common initial clinical manifestation, and about 15% of cases present metastasis at diagnosis. The treatment relies on surgical resection while the role of adjuvant chemotherapy and radiotherapy remains unclear. The prognosis for patients is generally poor, with a lethal outcome in 30% over a 24-month period. The authors report a case of a 62-year-old patient with the diagnosis of MTVT without a history of asbestos exposure. After surgical treatment, metastatic disease ensued. Chemotherapy was initiated, but could not be continued due to marked and fast clinical deterioration. The authors call attention to the difficulty of early diagnosis of MTVT due to a nonspecific clinical picture, the lack of action by the patient when the scrotal enlargement was first noticed, and the lack of tumor markers. Delayed diagnosis is definitely related to unfavorable prognosis.

Functional endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes secondary to endometritis.

OBJECTIVE: Functional polyps and chronic endometritis are among the most common abnormalities seen in the endometrium of patients with implantation failures and recurrent miscarriages. In this study we describe morphological vascular changes in endometrial samples from asymptomatic infertile patients and their association with chronic endometritis and polyp. STUDY DESIGN: We selected 435 asymptomatic infertility patients submitted to office-based diagnostic hysteroscopy and endometrial biopsy. We described vascular changes and searched for histologic signs of endometritis and functional polyps in the endometrial samples. We explored the associations between these conditions. RESULTS: Signs of endometritis, vascular changes and polyps were identified in 176 (40.5%), 168 (38.6%) and 102 (23.4%) cases, respectively. There was a significant association between endometritis and vascular changes. The more frequent vascular alteration (70%) was the hyaline thickening of vessels, a morphological pattern very similar to the thick-walled vessels of polyps. Polyps were associated with endometritis in 28 (27.4%) cases and with other vascular changes besides the vascular stalk in 14 (13.7%). All the polyps with vascular changes had histologic evidence of endometritis. There was a significant association between inflammatory phenomena and vascular changes, even among cases of polyps. CONCLUSIONS: Endometrial samples from infertile patients present a broad spectrum of vascular changes, most of them associated with endometritis. This association is also identified in functional polyps. Our results suggest that these alterations may be etiologically related. It is possible that the vessel axis of functional polyps actually may originate from the evolution of the vascular changes associated with endometritis. This would place functional polyps among the spectrum of inflammatory endometrial diseases.

Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast.

PURPOSE: To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS: We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS: There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.

Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast / Comparação do grau nuclear e perfil imunoistoquímico nos componentes in situ e invasivo de carcinoma mamário

PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS:There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.

OBJETIVO: Comparar características prognósticas e preditivas entre os componentes in situ e invasivo de carcinomas ductais da mama. MÉTODOS: Selecionamos 146 amostras mamárias consecutivas com carcinoma ductal in situ (CDIS) associado com carcinoma invasivo (CI) adjacente. Avaliamos grau nuclear e a expressão imunoistoquímica de receptor de estrogênio (RE), receptor de progesterona (RP), receptor do fator de crescimento epidérmico humano 2 (HER2), citoqueratina 5/6 (CK5/6) e o receptor do fator de crescimento epidérmico (EGFR) em ambos componentes, in situ e invasor, e a porcentagem de células marcadas pelo Ki-67 no componente invasivo. CDIS e CI foram classificados nos tipos moleculares, determinados pelo perfil imunoistoquímico, como luminal (RE/RP-positivo/HER2-negativo), triplo-positivo (RE/RP/HER2-positivo), HER2-puro (RE/RP-negativo/HER2-positivo) e triplo-negativo (RE/RP/HER2-negativo). A discriminação entre luminal A e Luminal B não foi feita por motivos estatísticos. Correlações entre as categorias dos dois grupos foram feitas pelo método de correlação de Spearman. RESULTADOS: Houve significante associação entre grau nuclear (p<0,0001), expressão de RE/RP) (p<0,0001), superexpressão de HER2 (p<0,0001), expressão de EGFR (p<0,0001) e perfil molecular (p<0,0001) entre os componentes in situ e invasivo. CK5/6 mostrou distribuição distinta em CDIS e CI, apresentando significante associação com o fenótipo triplo-negativo em CI, mas uma associação negativa ente os CDIS. CONCLUSÕES:Nossos resultados sugerem que as características prognósticas e preditivas clássicas dos CI estão já determinadas no estágio pré-invasivo da doença. Entretanto, o papel da CK5/6 no carcinoma invasivo pode ser diferente daquele das lesões precursoras.