Frédéric Buxant

Proliferating activity in columnar cell lesions of the breast

With the introduction of mammographic screening, columnar cell lesions (CCLs) are observed more and more frequently because they are often associated with microcalcifications. Until now, the proliferative activity of these lesions has not been previously evaluated. Ki67 index was performed by immunohistochemistry in CCLs without atypia [columnar cell change (CCC) n = 20 and columnar cell hyperplasia without atypia (CCH without atypia) n = 20], flat epithelial atypia (FEA DIN1A n = 20), low-grade intraductal carcinoma (DIN1C n = 20), high-grade intraductal carcinoma (DIN 2–3 n = 20). Adjacent terminal duct-lobular unit (TDLU) of normal breast tissue served as control. Ki-67 index is extremely low and close in CCLs without atypia (CCC mean 0.1% and CCH mean 0.76%) and paradoxically is lower than in normal TDLU (mean 2.4%) (p < 0.001). In the FEA, in comparison with normal TDLU and CCLs without atypia, the Ki67 is higher (mean 8.2%) (p < 0.001) but extremely close to those of DIN1C (mean 8.9%) (p = 0.6 NS). Lastly, the Ki67 index is higher in DIN 2–3 (mean 25.4%) than in CCLs without atypia and FEA (p < 0.001). CCLs are disparate lesions having in common cells with columnar configuration but different proliferative characteristics. These data represent findings of biological interest which could help us to better understand these controversial lesions.

Estrogen receptor, progesterone receptor, and glucocorticoid receptor expression in normal breast tissue, breast in situ carcinoma, and invasive breast cancer

Glucocorticoids (GCs) are used in cancer treatment to induce programmed cell death in transformed cells of the hematopoietic system and to lessen side effects. Moreover, GCs have been described not only as inhibitors of some chemotherapy or radiation-induced apoptosis, but also as inhibitors of cancer progression by down-regulation or up-regulation of different gene expressions. Recently, it has been suggested that GCs can attenuate estrogen responses through induction of expression and activity of the sulfotransferase. The presence or absence of glucocorticoid receptor (GR) in normal and abnormal breast tissue is thus interesting, and the aim of this study was to analyze the expression of GR during the progression of breast tissue. We tested by immunohistochemistry the expression status of estrogen receptor (ER), progesterone receptor (PR), and GR in normal breast parenchyma (n=49), ductal intraepithelial neoplasia (DIN) 1a (n=9), DIN 1b-1c (n=15), DIN 2-3 (n=21), and invasive breast carcinoma (n=39). The evaluation of GR expression was made by using the Allred score. All the normal parenchyma, DIN 1a, DIN 1b, and DIN 1c were ER-positive (ER+) and PR-positive (PR+). Seventeen of 21 DIN 2-3 and 30 of 39 invasive carcinomas were ER+/PR+. The other samples were ER-negative (ER−) and PR-negative (PR−). Moreover, all the ER−/PR− samples were GR-negative. Interestingly, we found a significant correlation between the histologic grade and the GR-negative tumors, and a percentage of positive patients presented with nuclear immunoreaction to GR, which decreases significantly with tumor histologic grade. Understanding the role of GCs in breast carcinoma is thus essential before continuing the widespread use of GCs combined with antineoplastic drugs or agents in the clinical management of women with breast cancer.

Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis

OBJECTIVE To analyze the expression of estrogen (ER) and progesterone (PR) receptors in the smooth muscle component (SMC) of deep infiltrating endometriosis (DIE). DESIGN A prospective clinical and pathologic study of 60 cases of DIE. SETTING University Hospital Department of Gynacology. PATIENT(S) Sixty patients with symptomatic DIE (uterosacral endometriosis n = 14; bladder endometriosis n = 10; colonic endometriosis n = 16; rectovaginal endometriosis n = 20). INTERVENTION(S) Laparoscopic surgery. MAIN OUTCOME MEASURE(S) The expression of ER and PR was studied by immunohistochemistry in the SMC directly around endometriotic foci and at distance (at least >1.5 cm) from them in correlation with proliferative and secretory phases of cycle. RESULTS The ER and PR were present in the SMC of DEI in each location excepting colonic endometriosis where ER were absent. Independently of cycles phases the PR were more abundant than ER. With the exception of rectovaginal endometriosis, where the ER and PR were more abundant in the proliferative than in the secretory phase, in other locations the ER and PR did not differ significantly with cycles phases. Last, if ER and PR were more abundant in SMC around endometriotic foci than at a distance from them. However, the difference was not significant. CONCLUSIONS Our data substantially confirm for the first time that in various forms of DIE, ER and PR are present not only in glands and stroma but also in the smooth muscle major histologic component of this disease.

Immediate surgical resection of residual microcalcifications after a diagnosis of pure flat epithelial atypia on core biopsy: A word of caution

The entity of pure flat epithelial atypia remains a challenge due to controversy of the surgical management of residual microcalcifications after core needle biopsies. This study aims to assess the morphological data observed in immediate surgical resection specimen of residual microcalcifications after a diagnosis of pure flat epithelial atypia on mammotome core biopsy. Sixty-two mammotome core biopsy with a diagnosis of pure flat epithelial atypia (flat epithelial atypia without associated atypical ductal hyperplasia, in situ and/or invasive carcinoma) were identified. From these 62 cases, 20 presented residual microcalcifications and underwent an immediate surgical excision after mammotome. Of the 20 patients with excised microcalcifications, 8 (40%)cases had residual pure flat epithelial atypia, 4 (20%) cases had atypical ductal hyperplasia, 4 (20%) cases had lobular in situ neoplasia, no lesions were retrieved in 4 (20%) case. None of the patients had either in situ ductal carcinoma and/or invasive carcinoma. Surgical resection of residual microcalcifications after the diagnosis of pure flat epithelial atypia on core needle biopsy remains still a debate. The present study shows no cases of in situ ductal and/or invasive carcinoma on immediate excision of residual microcalcifications after mammotome core biopsies.

Cervical response to vaccination against HPV16 E7 in case of severe dysplasia

OBJECTIVE To evaluate the tolerance to vaccination against human papillomavirus (HPV)16 E7 (in SB adjuvant ASO2B) and its histological and immunohistological effects on HPV16 associated high-grade cervical dysplasias associated with HPV16. STUDY DESIGN Five patients with histologically demonstrated severe cervical dysplasia (CIN3) HPV16 positive were injected three times before conization was performed 2 months after the first injection. We studied cytological, histological, proliferative pattern and immune profile before and after vaccination. The slides were compared with those obtained from non-injected patients. RESULTS The injections were well tolerated and the specimens displayed a limited regression of the lesions. Nevertheless, massive CD4 and CD8 T cell lymphocytic infiltration was noticed after vaccination. DISCUSSION We conclude that the vaccination we used provides an obvious immune histological reaction in the HPV infected cervix and that the 2 months delay before the final step (conization) is done is probably too short.

Ki-67 Immunostaining Activity is Higher in Positive Axillary Lymph Nodes than in the Primary Breast Tumor

AbstractBackground. The monoclonal antibody Ki-67 allows to investigate the proliferative activity of tumor and is a clinically useful marker to characterize breast cancer. In this study, we have compared Ki-67 activity in 38 primary breast tumors and in their respective positive axillary lymph nodes (ALNs). Methods. Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 38 nodes positive breast carcinomas and in their respective positive ALNs. Statistical analysis was performed with the Students t-test (2-tailed) for equality of means. Results. The proliferation index measured by Ki-67 expression was significatively higher (p < 0.02) in ALN than in the primary tumor (29.8% v.s. 21.8%). Conclusion. These results strongly suggest a higher proliferation and perhaps aggressivity of metastatic neoplastic cells when compared with their respective primary tumor. Perhaps, in the future, these differences in proliferation behavior might be taken into account when considering the choice of the adjuvant therapy.

Low-grade adenosquamous carcinoma of the breast—A case report with a BRCA1 germline mutation

Breast cancers occurring in women with germline BRCA1 mutations tend to fall into the category of triple-negative or basal-like phenotypes, such as metaplastic carcinoma. Low-grade adenosquamous carcinoma of the breast is a rare variant of metaplastic carcinoma. We present the case of a 49-year-old woman with a past medical history of invasive ductal breast carcinoma 13 years ago, and who was recently diagnosed as having a low-grade adenosquamous carcinoma in the same breast. Genetic analysis of blood DNA revealed a BRCA1 mutation. To our knowledge, BRCA1 mutation in association with a low-grade adenosquamous carcinoma of the breast has not yet been reported. Thus, it may be important to consider the possibility of an association, but supplemental studies are needed.

Laminin-5γ2 chain expression in cervical intraepithelial neoplasia and invasive cervical carcinoma

Background.  To analyze the expression of laminin‐5γ2 chain, a protein which plays a major role in keratinocyte migration, in cervical intraepithelial neoplasia (CIN), and invasive cervical carcinoma associated with high‐risk oncogenic human papillomaviruses (HR‐HPVs).

Antiproliferative effect of dexamethasone in the MCF-7 breast cancer cell line

Glucocorticoids (GCs) are used in the treatment of cancer to induce programmed cell death in the transformed cells of the hematopoietic system and to reduce side effects. Additionally, GCs are described as an inhibitor of certain chemotherapy or radiation-induced apoptosis and also an inhibitor of cancer progression by downregulating or upregulating the expression of several genes. The present study used immunofluorescence to investigate the presence of the glucocorticoid receptor (GR) in MCF-7 cells, and the cell culture growth was determined by cell counting the number of cells following exposure to GC and/or dexamethasone (Dex). The presence and immunoreactivity of the GR were confirmed, and treatment with Dex (10−8–10−7 M) caused an inhibitory effect (30–35%) on the proliferative activity of the MCF-7 cells. This growth inhibitory effect was possibly produced by the pro-apopotic effect of Dex. Since Dex is administered systematically prior to breast cancer chemotherapy, the possible interactions between these drugs require further investigation.

Omental trophoblastic implants after surgical management of ectopic pregnancy

Peritoneal implants secondary to a tubal ectopic pregnancy or extratubal omental secondary trophoblastic implants (ESTI) are a rare entity often underestimated or unknown. It can be responsible of rising in the ß-hCG titer after salpingectomy for ectopic tubal pregnancy. Moreover, implants on the omentum are exceptional. This particular localization is exceptional and its physiopathology, diagnosis, surgical management and follow-up are discussed in this paper.