Immunosuppressive therapy before and during pregnancy may improve obstetric outcomes in pregnancy complicated by dermatomyositis with anti-MDA-5 antibody positivity: A case report.

Dermatomyositis (DM) is one of the most common autoimmune rheumatic diseases affecting women of childbearing age. Pregnancy may lead to exacerbation of DM, especially of DM with anti-melanoma differentiation-associated gene (MDA) 5 antibody positivity, leading to a poor obstetric outcome. Here, we report consecutive pregnancies complicated by DM with anti-MDA-5 antibodies. A 32-year-old pregnant woman, gravida 3 para 1, presented with fetal growth restriction. Emergency cesarean section was performed because of non-reassuring fetal status at 28 weeks of gestation. Two days postpartum, the patient's hand eczema had worsened and she was diagnosed with DM with MDA-5 antibody positivity. Immunosuppressive therapy using corticosteroids combined with tacrolimus was immediately started, suppressing the DM symptoms. Eighteen months later, she became pregnant again but was then negative for anti-MDA-5 antibodies while continuing immunosuppressive therapy. During pregnancy, the titer of the antibody gradually increased, peaked in the second trimester and declined to near normal range through the third trimester. A male infant weighing 2418 g was delivered at 38 weeks of gestation. Our case demonstrates that controlling of DM activity using immunosuppressive treatment before and during pregnancy may be beneficial to obstetric outcomes.

Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers.

BACKGROUND: The ABCD stratification [(combination of serum pepsinogen (PG) levels and titers of antibody (immunoglobulin G, IgG) against Helicobacter pylori (H. pylori)] is effective for the classification of individuals at risk of developing gastric cancer (GC). The Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a Cancer/Testis antigen frequently expressed in GC. AIM: To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC. METHODS: We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors. The levels of serum PG I/PG II and IgG against H. pylori were measured. According to their serological status, the patients were classified into the four groups of the ABCD stratification. RESULTS: Of the 77 examined patients, 63 (81.8%) expressed KK-LC-1. The IgG titers of H. pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1 (P = 0.0289 and P = 0.0041, respectively). The expression of KK-LC-1 in group C [PG method (+)/H. pylori infection (+)] was as high as 93.9% high. KK-LC-1 was also detected in group A [-/-]. CONCLUSION: The KK-LC-1 expression in GC was associated with H. pylori infection and atrophic status, so that, KK-LC-1 may be a useful marker for the diagnosis of GC.

Lymph node metastasis and high serum CEA are important prognostic factors in hormone receptor positive and HER2 negative breast cancer.

In recent years, treatment options for breast cancer have increased, and prognosis has improved since the 1990s. The present study examined the prognosis for recurrence of breast cancer between 2006 and 2009, in comparison with the results of past treatments, and sought to guide future treatment strategies by elucidating present prognostic factors. A total of 662 patients with breast cancer stage 0-III who underwent surgery at Kitasato University Hospital between January 2006 and March 2009 were included. Cases were classified into four subtypes, based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2 (HER2). Factors associated with recurrence and prognosis were then examined. The 5-year recurrence-free survival (RFS) was 94.9% and the 5-year disease-specific survival (DSS) was 98.4%. Factors related to RFS were pathological lymph node (pN) positive [hazard ratio (HR)=2.85, P=0.001], clinical lymph node (cN) positive (HR=2.28, P<0.01), and hormone receptor negative (HR=1.83, P<0.05). Factors associated with DSS were cN positive (HR=4.55, P<0.01), pN positive (HR=3.40, P<0.05), higher preoperative serum carcinoembryonic antigen (CEA) (HR=3.04, P<0.05), and hormone receptor negative (HR=2.32, P<0.05). In the hormone receptor positive HER2 negative, cN-positive/pN-positive breast cancer group, RFS and DSS were poorer compared with the other groups. In this group, preoperative high CEA level was a poor prognostic factor. The prognosis for hormone receptor positive HER2-negative breast cancer has improved significantly since the 1990s. On the other hand, the prognosis for cN-positive/pN-positive breast cancer was poor. Pre-treatment serum CEA positive cases exhibited a particularly poor prognosis.

Correlation Between Expression of the Cancer/Testis Antigen KK-LC-1 and Helicobacter pylori Infection in Gastric Cancer.

BACKGROUND/AIM: Our previous study indicated that Kita-kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) expressed in 82% of gastric cancer cases. Here, we investigated the relationship between KK-LC-1 expression and Helicobacter pylori infection in Japanese patients with gastric cancer. PATIENTS AND METHODS: We examined CTA expression in 25 surgical gastric cancer specimens and anti-H. pylori IgGs in the serum of each patient. RESULTS: KK-LC-1 was expressed in 80% of tumor samples, markedly higher than melanoma antigen gene (MAGE)-A1, MAGE-A3, MAGE-A4, synovial sarcoma, X breakpoint 4 (SSX4) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1). Anti-H. pylori IgG titers from the KK-LC-1-positive patients were significantly higher (67.5±7.6) than those from KK-LC-1-negative patients (15.8±7.5, p<0.01) although there were no significant differences between patients positive and negative for MAGE-A1, -A3 and-A4, SSX4 and NY-ESO-1. CONCLUSION: As far as we are aware, this is the first report of a correlation between a carcinogen and CTA expression in clinical samples. KK-LC-1 was frequently expressed in gastric cancer caused by H. pylori infection. The risk diagnosis for gastric cancer might be more accurate if KK-LC-1 expression status were also considered.

Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen.

AIM: To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors. METHODS: Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS: The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion (MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion (MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage (36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NY-ESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1 (MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION: The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

BRCAness and Prognosis in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

BRCAness is defined as the set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation or deletion, results in DNA repair deficiency. In the present study, we addressed BRCAness, therapeutic efficacy, recurrence, and survival in patients with triple negative breast cancer (TNBC) who were treated with neoadjuvant chemotherapy at Kitasato University Hospital, Japan, between April 2006 and October 2012. BRCAness was determined by preoperative core needle biopsy (CNB) specimens and surgical specimens. Assay was performed using Multiplex Ligation-dependent Probe Amplification (MLPA) with P376-B2 BRCA1ness probemix (MRC-Holland, Amsterdam, The Netherlands). The relative copy number ratio of each sample was compared to Human Genomic DNA (Promega, Madison, WI, USA) as reference samples was calculated with Coffalyser.NET default settings. The BRCAness score was calculated with the relative copy number ratio of various DNA sequences. Values of 0.5 or more were determined as the BRCA1-like Type (BRCAness) and those of less than 0.5 as the Sporadic Type to analyze pathological complete response (pCR) rate, recurrence, and survival. pCR (ypT0/Tis/N0) was observed in 15 patients (pCR rate: 37.5%). These patients had no recurrence. Twelve patients recurred, 8 died from breast cancer. The BRCA1-like Type were 22 and Sporadic Type were 18 in CNB specimens. No major differences were observed between the BRCA1-like Type and Sporadic Type with pCR rate, recurrence rate and survival. Twenty four surgical specimens of non-pCR patients were available and 9 were BRCA1-like Type, who had more recurrences (7/9 vs. 5/15), and their relapse-free survival was also lower (p<0.05) than that of Sporadic Type. Seven BRCA1-like Type patients remained BRCA1-like Type in surgical specimens, were worse in recurrence (p<0.01) and survival (p<0.05) compared with 6 patients whose BRCA status in surgical specimens turned to Sporadic Type. New clinical trials assessing the true recurrence (TR) rate of BRCA-type patients are expected since neither platinum-containing drugs nor poly (ADP-ribose) polymerase (PARP) inhibitors are effective against tumors with nonfunctional BRCA genes.

[A Case of Advanced Malignant Melanoma of the Esophagus with Distant Metastases].

A 65-year-old woman with dysphagia visited our outpatient clinic. Esophagogastric endoscopy revealed a number of black-brown, irregularly elevated lesions covering the mucosal layer of nearly the entire esophagus. Following a series of examinations including histological examinations of the biopsies and whole body FDG-PET/CT, the patient was diagnosed with malignant melanoma primarily of the esophagus with metastasis to the distant lymph nodes, duodenum, pancreas head, and left brachial bone [cT3N3M1, StageIVb]. Since surgicalresection was not indicated, dacarbazine (DTIC: 1,000mg/m² body surface area)was intravenously administered 7 times every 3 weeks on an outpatient basis. However, the disease was progressive and metastasized to the stomach, duodenum, and small intestine, and finally to the brain. The patient died 8 months after the diagnosis was made. Malignant melanoma of the esophagus is a relatively rare pathology, and no reliable therapeutic modalities have been established yet. Based on the present case, the effectiveness of DTIC in an advanced case is proposed to be limited. In addition, whole body FDG-PET/CT is very useful for detecting metastatic lesions that could be missed otherwise.

Frequent High Expression of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) in Gastric Cancer.

BACKGROUND: The tumor-associated antigen Kita-Kyushu lung cancer antigen-1 (KK-LC-1) has been reported as not being expressed in normal tissues, except for the testis, and in the setting of non-small cell lung cancer. The present study demonstrated that KK-LC-1 is expressed in gastric cancer. MATERIALS AND METHODS: We analyzed the expression of KK-LC-1 and cancer/testis antigens (CTAs) in surgical specimens of 49 gastric carcinomas. The expression of KK-LC-1 and CTAs was assessed using reverse transcription-polymerase chain reaction. RESULTS: KK-LC-1 expression was observed in gastric carcinomas. The number of lesions with expression of KK-LC-1, Melanoma antigen gene encoding-A1 (MAGE-A1), MAGE-A3 and New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) was 40 (81.6%), 17 (34.7%), 22 (44.9%) and 8 (16.3%) out of the 49 specimens, respectively. CONCLUSION: KK-LC-1 should be categorized as a CTA. The frequency of KK-LC-1 expression was higher than that of the other CTAs. KK-LC-1 might be a useful target for immunotherapy and in diagnosis of gastric cancer.