Corynebacterium kroppenstedtii in granulomatous mastitis: Analysis of formalin-fixed, paraffin-embedded biopsy specimens by immunostaining using low-specificity bacterial antisera and real-time polymerase chain reaction.

Granulomatous mastitis (GM) is a rare inflammatory disease of the post-lactation breast, clinically mimicking breast cancer. GM is microscopically characterized by formation of epithelioid granulomas and abscess (suppurative granulomas) with lipid droplet-centered inflammation. Corynebacterium kroppenstedtii (Ck) is known as a causative bacterium of GM, and identification of Ck infection within the lesion should thus be essential for confirming the diagnosis. In the present study, we analyzed formalin-fixed, paraffin-embedded (FFPE) biopsy specimens of a total of 18 GM lesions with immunostaining and real-time PCR for Ck genome. Widely cross-reactive rabbit antisera against Bacillus Calmette-Guerin (BCG), Bacillus cereus, Treponema pallidum and Escherichia coli were chosen. With real-time PCR, Ck genome was demonstrated in 7 of 18 GM lesions. Immunohistochemically, the low-specificity antisera reacted with the cytoplasm of phagocytes and/or granuloma-engulfed lipid droplets in 12 of 18 GM lesions. Antigenic positivity was observed in the following order: BCG > B. cereus > T. pallidum > E. coli. Real-time PCR using DNA extracted from FFPE sections was useful but not consistent for identifying the Ck genome in GM, while immunostaining using cross-reactive antisera against four kinds of bacteria was not Ck-specific but was applicable to visualizing bacterial infection within the GM lesions.

Multimodality therapeutic outcomes in anaplastic thyroid carcinoma: improved survival in subgroups of patients with localized primary tumors.

BACKGROUND: The aim of the present study was to investigate the role of a multimodality treatment for anaplastic thyroid carcinoma (ATC). METHODS: Clinical data of 40 consecutive patients treated between 1985 and 2009 were retrospectively analyzed. RESULTS: The median survival time (MST) stratified by clinical stage was 6.0 months for stage IVB and 4.2 months for stage IVC. When the stage IVB patients were classified into 2 groups (IVB-a and IVB-b) in accord with the extent of involvement of the tumor, the MST of the patients with IVB-a (9.6 months) was significantly longer than that of patients with IVB-b (4.0 months) (p < .05). The MST of the patients treated with surgery followed by radiation and chemotherapy (13.7 months) tended to be longer compared with the patients treated with 2 or fewer modalities. CONCLUSION: The patients with a less-invasive primary tumor may gain a survival benefit from aggressive multimodality therapeutic approaches.

[A retrospective study of high-dose toremifene treatment for patients with aromatase inhibitor refractory advanced or metastatic hormone receptor-positive breast cancer].

Aromatase inhibitors (AI) have largely replaced tamoxifen as the first-line of treatment for postmenopausal women with advanced or metastatic hormone-receptor-positive breast cancer. However, there is no established strategy for treating AI refractory cases. In this study, we investigated the efficacy of high-dose Toremifene therapy (HD-TOR). From January 2001 through April 2010, nineteen patients received 120 mg of TOR daily. The overall response rate was 36.8% (CR; 1, PR; 6), and the clinical benefit was 47.4%. The clinical benefit rate to each of the metastatic organs were: lung, 42.9%; bone, 13%; liver, 25%; and lymph node, 40%. A higher clinical benefit rate was observed in lung or lymph node metastases. The clinical benefit rate of HD-TOR as first to third-line therapy was 50%, which was more effective than that of fourth-line therapy. Our data suggests that HD-TOR may be one of the effective treatment strategies for patients with AI refractory advanced or metastatic hormone receptor-positive breast cancer.

CSLEX (Sialyl Lewis X) is a useful tumor marker for monitoring of breast cancer patients.

BACKGROUND: CSLEX is a type II carbohydrate antigen that interacts with the CSLEX-1 monoclonal antibody. CSLEX in combination with carbohydrate antigen 15-3 may be more useful than Carcinoembryonic Antigen with carbohydrate antigen 15-3 as tumor markers for monitoring of breast cancer. METHODS: The serum levels of tumor markers, including CSLEX, were measured in 480 consecutive breast cancer patients with or without metastasis who visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. RESULTS: Serum levels of each of the tumor markers correlated significantly with the status of metastasis (P < 0.01). Combinations of Carcinoembryonic Antigen and carbohydrate antigen 15-3, Carcinoembryonic Antigen and Nation Cancer Center-Stomach-439, Carcinoembryonic Antigen and CSLEX, carbohydrate antigen 15-3 and Nation Cancer Center-Stomach-439, and carbohydrate antigen 15-3 and CSLEX levels also correlated significantly with the status of metastasis (P < 0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were almost the same for CSLEX and Nation Cancer Center-Stomach-439, which are both type II carbohydrate antigens. The cutoff indexes of serum CSLEX and Nation Cancer Center-Stomach-439 for detection of breast cancer metastasis were 38.8 ± 52.7-fold and 22.1 ± 27.8-fold, respectively (P = 0.16). CONCLUSIONS: These data suggest that the diagnostic values of CSLEX and Nation Cancer Center-Stomach-439 are similar in single or combined use. However, the cutoff index of serum CSLEX tended to be higher than that of Nation Cancer Center-Stomach-439, which may make CSLEX more useful for detection of breast cancer metastasis.

Significance of tumor-associated stroma in promotion of intratumoral lymphangiogenesis: pivotal role of a hyaluronan-rich tumor microenvironment.

Stromal cells, together with extracellular matrix components, provide a tumor microenvironment that is pivotal for cancer cell growth and progression. In our previous study using a conditional transgenic mouse model of breast cancer, the overproduction of hyaluronan, a major extracellular constituent, accelerated tumor angiogenesis through stromal cell recruitment. This finding led us to investigate the role of hyaluronan in the lymphatic vessel system. Here, we have found that microenvironmental hyaluronan promoted tumor lymphangiogenesis concurrently with the formation of stromal structures. Additionally, lymphatic vessels frequently penetrated and accumulated into stromal compartments, and up-regulation of vascular endothelial growth factor-C and -D was detected at tumor-stromal interfaces. To assess the contribution of stromal cells to lymphangiogenesis in vivo, we established tumor-associated fibroblasts from hyaluronan-overproducing mammary tumors and implanted them together with carcinoma cells from control tumors or MCF-7 human breast carcinoma cells in nude mice. Carcinoma cells grew rapidly in association with marked stromal reactions and lymphangiogenesis. Without the stromal cells, however, the tumors developed slowly with less stroma and lymphatic vessels. These findings underline the significance of tumor-associated stroma in the promotion of intratumoral lymphangiogenesis and suggest a pivotal role for the hyaluronan-rich tumor microenvironment.