TM4SF1, a novel primary androgen receptor target gene over-expressed in human prostate cancer and involved in cell migration.

BACKGROUND: The Androgen Receptor (AR) plays a key role in controlling prostate gland homeostasis and contributes to prostate carcinogenesis. The identification of its target genes should provide new candidates that may be implicated in cancer initiation and progression. METHODS: Transcriptomic experiments and chromatin immunoprecipitation were combined to identify direct androgen regulated genes. Real-time quantitative PCR (RT-qPCR) analyses were performed to measure TM4SF1 mRNA levels in prostate cancer and benign prostatic hyperplasia (BPH) specimens. Immunohistochemical methods were used to compare TM4SF1 protein expression profiles in the same cohort. A targeted siRNAs knockdown strategy was used, prior to wound healing assays, to analyze the role of TM4SF1 in cell migration in vitro. RESULTS: We demonstrate for the first time that TM4SF1 is a direct target gene of the AR, a transcription factor of the steroid nuclear receptor family. A functional androgen response element was identified in the promoter region of the gene. In addition, TM4SF1 mRNA expression was higher in cancer samples compared to BPH tissues. The TM4SF1 protein mediates cell motility of prostate cancer cells where it is predominantly localized in the cytoplasm, in contrast to its apical membrane localization in normal prostate epithelial cells. CONCLUSIONS: Our results reveal a novel function for TM4SF1 in AR signaling. The TM4SF1 mRNA expression is higher in prostate cancer tissues as compared to BPH samples. Inhibition of cell migration after targeted knockdown of TM4SF1 protein expression suggests its contribution to prostate cancer cell metastasis.

Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer?

BACKGROUND: Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients. METHODS: Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node-positive breast cancers entered the study (median follow-up, 126 months). RESULTS: LVI was present in 46% of tumors and was associated with age < or = 40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER-2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER-2/neu-negative/hormone receptor-positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5-years metastasis-free survival ranging from 100% if no factors (n = 25) to 89% +/- 2% if 1 or 2 factors (n = 186) and 67% +/- 6 if 3, 4, or 5 factors (n = 76) were present (P < .001). CONCLUSIONS: LVI is an independent prognostic factor in lymph node-positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting.

Nonconventional papillary thyroid carcinomas with pleomorphic tumor giant cells: a diagnostic pitfall with anaplastic carcinoma.

The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

[Isolated testicular mass revealing a metastasis of prostate adenocarcinoma]. / Masse testiculaire unique révélant une métastase d'un adénocarcinome prostatique.

A testicular mass on a patient over 50 years should be considered as a metastasis, a lymphoma or a spermatocytic seminoma. Testicular metastases are rare, representing about 1 % of all testicular tumors. Prostate is the most common primary site, with less than 100 reported cases in the literature. They are most often incidentally discovered tumors, after bilateral orchiectomy for hormonal management of prostate carcinoma or at autopsy. Metastases revealed by a testicular mass are very rare. We report the original case of an 80-year-old patient with a left testicular mass indicating a metastasis of a prostate carcinoma diagnosed six years earlier. No other metastatic localization was found.

[Lymphomatoid granulomatosis after treatment of an acute myeloid leukemia]. / Granulomatose lymphomatoïde dans les suites d'une leucémie aiguë myéloïde.

We report a case of lymphomatoid granulomatosis (LG), arising in a 60-year-old man in the setting of an acute myeloid leukemia. LG is a rare Epstein Barr virus (EBV) lymphoproliferative disorder, generally occurring in a context of immunodeficiency. Patients usually present with respiratory symptoms and bilateral pulmonary nodules. Histologically LG is characterized by an angiocientric and angiodestructive lymphoproliferation of B/EBV+ cells admixed with numerous reactive T cells. The differential diagnosis mainly includes pulmonary vasculitis and Hodgkin's lymphoma. The outcome of this lymphoproliferation is highly variable, ranging from an indolent process to an aggressive large cell lymphoma.