Behzad, Masumeh Maleki; Asnafi, Ali Amin; Jaseb, Kaveh; Jalali Far, Mohammad Ali; Saki, Najmaldin
doi: 10.1111/apm.12755pmid: 28960510
Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto‐Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990–2016) of English‐language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self‐tolerance dysfunction, as well as induction of Auto‐Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients.
Dematei, Anderson; Fernandes, Rúben; Soares, Raquel; Alves, Helena; Richter, Joachim; Botelho, Monica C.
doi: 10.1111/apm.12756pmid: 28960560
Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis‐associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis.
Hong, Soon Auck; Kim, Ki Hong; Lee, Tae Jin; Park, Eon Sub; Kim, Mi Kyung; Myung, Soon Chul
doi: 10.1111/apm.12749pmid: 28885732
The purpose of this study was to clarify the role of human beta defensin‐1 (hBD‐1) in predicting PAC in morphologically normal prostate glands. In total, 25 patients with a negative initial biopsy for PAC and diagnosed as PAC positive in subsequent biopsies performed within 1 year of the initial biopsy were included. As a control group, 22 patients negative for PAC in at least three consecutive histologic examinations were selected. Expression of hBD‐1 was analyzed separately via immunohistochemistry in paired cores of non‐neoplastic gland and PAC in the false‐negative group and control group. Loss of hBD‐1 expression was observed in 95.6% and 90.0% PAC cases with Gleason Patterns 3 and 4 in repeat biopsies, respectively. hBD‐1 loss of basal cells in 40 (85.1%) previous non‐neoplastic biopsy cores in the false‐negative group was observed, in contrast to preserved basal cell expression of hBD‐1 in 64 (72.7%) biopsy cores in the control group (p = 0.001). Multivariate logistic regression analysis showed that hBD‐1 basal cell loss (≥20% of prostatic glands in total cores) is an independent factor for predicting PAC (odds ratio: 4.739, confidence interval: 1.093–20.554, p = 0.038). hBD‐1 loss of basal cells is a useful indicator to identify extremely high‐risk patients with initially negative biopsy.
Zhao, Jinzhu; Yuan, Wei; Tao, Chunsheng; Sun, Peifeng; Yang, Zaixing; Xu, Weidong
doi: 10.1111/apm.12757pmid: 28971528
The aim of this study was to evaluate the polarization of peripheral blood monocytes in the patients with ankylosing spondylitis (AS) and to determine the correlations between monocyte polarization and inflammation and structural damage. A total of 120 AS patients, 50 rheumatoid arthritis (RA) patients and 100 healthy controls were enrolled in the study. M1 (CD68+CD192+) and M2 (CX3CR1+CD163+) monocytes were characterized by flow cytometry. Demographic, clinical, radiographic and laboratory data were collected and analyzed. A large increase in M2 (CX3CR1+CD163+) monocytes was observed in AS, and M2/M1 ratio was 7.18 ± 6.12, 2.54 ± 3.14 and 35.61 ± 20.04 in control, RA and AS, respectively. The M2/M1 ratio correlated with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (r = 0.565; p < 0.001), ESR (r = −0.321; p < 0.001, CRP (r = −0.265; p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (r = −0.201; p = 0.028). Anti‐TNF‐α therapy induced a significant reduction in the percentage of M1 monocyte, ESR, CRP and BASDAI in AS patients. The present results demonstrated that M2 type polarized monocytes are predominant in the peripheral blood in AS and the M2/M1 ratio is correlated with structural damage (mSASSS), inflammatory biomarkers (ESR and CRP) and BASDAI.
Oh, Hyeon Jeong; Kim, Jung Ho; Lee, Tae Hun; Park, Hye Eun; Bae, Jeong Mo; Lee, Hye Seung; Kang, Gyeong Hoon
doi: 10.1111/apm.12770pmid: 28971530
The aim of this study is to establish heat shock protein 110 (HSP110) as a prognostic biomarker of colorectal carcinomas (CRCs) with microsatellite instability‐high (MSI‐H) by considering the intratumoral heterogeneity of HSP110 expression. We performed whole‐section immunohistochemistry (IHC) for wild‐type HSP110 (HSP110wt) in 164 MSI‐H CRCs. The intensity of the HSP110wt expression in tumor cells was semiquantitatively scored (0/1/2/3), and the HSP110wt expression status of each tumor was classified as low or high using the following four scoring criteria: H‐score, dominant intensity score, lowest intensity score, and highest intensity score. Among the four criteria, only the dominant intensity score‐based dichotomous classification of HSP110wt expression was significantly associated with a difference in disease‐free survival (log‐rank p = 0.035) in 164 MSI‐H CRCs. The HSP110wt‐low MSI‐H CRCs were significantly correlated with larger deletions in the HSP110 T17 mononucleotide repeat (≥4 bp; p < 0.001). In conclusion, the dominant intensity score‐based assessment of HSP110wt IHC can be a simple and useful method for the prognostic stratification of MSI‐H CRCs. It is expected that HSP110wt IHC may be used to identify a subgroup of MSI‐H CRCs with poor prognosis and/or candidates for further treatment, such as immunotherapy using immune checkpoint inhibitors in MSI‐H CRCs.
Visser, Nicole C.M.; Werner, Henrica M.J.; Krakstad, Camilla; Mauland, Karen K.; Trovik, Jone; Massuger, Leon F.A.G.; Nagtegaal, Iris D.; Pijnenborg, Johanna M.A.; Salvesen, Helga B.; Bulten, Johan; Stefansson, Ingunn M.
doi: 10.1111/apm.12774
Wong, Kah Keng; Hussain, Faezahtul Arbaeyah; Loo, Suet Kee; López, José I.
doi: 10.1111/apm.12775pmid: 28972294
Spermatogenesis‐associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non‐malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non‐malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non‐malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty‐nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H‐score) was not associated with overall survival or disease‐specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease.
Kimura, Koji; Kobayashi, Daigo; Hatoyama, Saori; Yamamoto, Mizuki; Takayanagi, Risa; Yamada, Yasuhiko
doi: 10.1111/apm.12754pmid: 28913867
The associations between the efficacy of IgG reagents and the FCGRIIIa‐158V/F polymorphism (rs396991) have been investigated. Although the genotype frequencies in healthy Japanese have been reported, those have varied, as one study reported that the proportions of V/V, V/F, and F/F were 59.1%, 38.6%, and 2.3%, respectively, while another study found that they were 4%, 44%, and 52%, respectively. However, there are no known investigations of the association between the antibody‐dependent cellular cytotoxicity (ADCC) activity of adalimumab (ADA), an IgG reagent, in combination with FcγRIIIa and the polymorphism. In this study, we analyzed healthy Japanese to clarify genotype frequency using a direct sequence method. In addition, we examined the association between the ADA‐mediated ADCC activity and the polymorphism. Our results showed that the frequencies of the V/V, V/F, and F/F genotypes in healthy Japanese were 9.2%, 39.8%, and 51.0%, respectively. The average activity of ADA‐mediated ADCC was 25.0%, 19.0%, and 13.3% in the V/V, V/F, and F/F genotypes, respectively. Then, the ADCC activity of V/V was significantly higher than that of F/F (p < 0.05) in therapeutic concentration. The differences in therapeutic effect of ADA among individuals can be explained, in part, by ADCC activity via the FCGRIIIa‐158V/F polymorphism.
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Vascular invasion (VI) is a well‐established marker for lymph node metastasis and outcome in endometrial cancer. Our study explored whether specific types of VI, defined as lymphatic (LVI) or blood vessel invasion (BVI), predict pattern of metastasis. From a prospectively collected cohort, we conducted a case–control study by selecting three groups of endometrial cancer patients (n = 183): 52 with positive lymph nodes at primary surgery, 33 with negative nodes at primary surgery and later recurrence and death from disease, and 98 with negative nodes and no recurrence. All patients underwent hysterectomy with lymphadenectomy. Immunohistochemical staining with D2‐40 and CD31 antibodies was used to differentiate between BVI and LVI. By immunohistochemical staining, detection of VI increased from 24.6 to 36.1% of the cases. LVSI was significantly more often seen in patients with positive lymph nodes compared with patients with negative nodes (p = 0.001). BVI was significantly more often seen in node‐negative patients with recurrence compared with node‐negative patients without recurrence (p = 0.011). In multivariable analysis, BVI, age, and tumor grade were predictors separating patients with and without recurrence. Lymph node–positive patients showed more often LVI compared with lymph node–negative patients, while BVI seems to be a predictor for recurrent disease.