MARCKS as a Potential Therapeutic Target in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is the most pro-metastatic form of breast cancer (BC). We previously demonstrated that protein overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein was associated with shorter survival in IBC patients. MARCKS has been associated with the PI3K/AKT pathway. MARCKS inhibitors are in development. Our objective was to investigate MARCKS, expressed preferentially in IBC that non-IBC (nIBC), as a novel potential therapeutic target for IBC. The biologic activity of MPS, a MARCKS peptide inhibitor, on cell proliferation, migration, invasion, and mammosphere formation was evaluated in IBC (SUM149 and SUM190) and nIBC (MDA-MB-231 and MCF7) cell lines, as well as its effects on protein expression in the PTEN/AKT and MAPK pathways. The prognostic relevance of MARCKS and phosphatase and tensin homolog (PTEN) protein expression as a surrogate marker of metastasis-free survival (MFS) was evaluated by immunohistochemistry (IHC) in a retrospective series of archival tumor samples derived from 180 IBC patients and 355 nIBC patients. In vitro MPS impaired cell proliferation, migration and invasion, and mammosphere formation in IBC cells. MARCKS inhibition upregulated PTEN and downregulated pAKT and pMAPK expression in IBC cells, but not in nIBC cells. By IHC, MARCKS expression and PTEN expression were negatively correlated in IBC samples and were associated with shorter MFS and longer MFS, respectively, in multivariate analysis. The combination of MARCKS-/PTEN+ protein status was associated with longer MFS in IBC patient only (p = 8.7 × 10-3), and mirrored the molecular profile (MARCKS-downregulated/PTEN-upregulated) of MPS-treated IBC cell lines. In conclusion, our results uncover a functional role of MARCKS implicated in IBC aggressiveness. Associated with the good-prognosis value of the MARCKS-/PTEN+ protein status that mirrors the molecular profile of MPS-treated IBC cell lines, our results suggest that MARCKS could be a potential therapeutic target in patients with MARCKS-positive IBC. Future preclinical studies using a larger panel of IBC cell lines, animal models and analysis of a larger series of clinical samples are warranted in order to validate our results.

Ovarian ALK+ diffuse large B-cell lymphoma: a case report and a review of the literature.

Through this case presentation and a review of the literature, we aim to describe clinical and pathologic features and to distinguish the outcome of these tumors. A 25-year-old woman presented with pelvic pain and an iliac mass. Workup revealed a 53-mm cystic partitioned mass of the left ovary infiltrating the left sacrum. She underwent a left adnexectomy. Gross examination revealed a ruptured ovarian mass. When dissected, it showed grayish cerebroid aspects. Histologic examination revealed a malignant tumor proliferation of the diffuse large cells. An immunohistochemical analysis showed negative results for PLAP, αFP, ßHCG, CD117, CK20, and CD30. It also showed lack of B markers and T marker (CD3) and an expression of CD138 and anaplastic lymphoma kinase. The patient was treated by 6 cycles of CHOP chemotherapy and a pelvic radiotherapy. She presented with a 15-cm splenomegaly 26 months later and died of febrile neutropenia. Most patients follow an aggressive disease and are unlikely to respond to the standard.

[Endometrial atypical complex hyperplasia with extensive squamous metaplasia: two cases]. / L'hyperplasie complexe atypique (HCA) de l'endomètre avec métaplasie malpighienne (MM) extensive. A propos de deux observations.

We report two cases of endometrial atypical complex hyperplasia with an extensive squamous hyperplasia occurring in two women aged 48 and 31 years old. The histological study showed an increase in the gland to stroma ratio with a false crowding aspect due to an extensive area of squamous metaplasia; some metaplastic areas were centered by necrosis. There was glandular cytologic atypia. Histologic examination is necessary to confirm the diagnosis and to definitively rule out adenocarcinoma.