Metastasis-associated colon cancer-1 is a novel prognostic marker for cervical cancer

Aims: To investigate metastasis associated in colon cancer 1 (MACC1) expression in cervical cancer. Methods: One hundred and four paraffin-embedded cervical cancer specimens were immunohistochemically analyzed for MACC1 expression. The expression of MACC1 in 8 pairs of cervical cancer and adjacent normal cervical tissues were detected by Real-time PCR. Results: MACC1 expression was upregulated in cervical cancer tissues compared with adjacent normal cervical tissues. Patients with higher MACC1 expression had shorter overall survival time, whereas those with lower ASAP1 expression survived longer (P = 0.029). Moreover, high expression of MACC1 was correlated with FIGO stage (P = 0.039) and lymph nodes metastasis (P = 0.003) of this disease. Multivariate analysis revealed that MACC1 was an independent prognostic factor (P = 0.043) for the overall survival of cervical cancer patients. Conclusion: Our study suggests that MACC1 may contribute to tumor development and progression in cervical cancer, and that MACC1 could be a useful marker for the prognosis of cervical cancer.     

Podoplanin: a novel diagnostic immunohistochemical marker

Podoplanin is a transmembrane mucoprotein recognized by the recently commercially available D2-40 monoclonal antibody. Recent investigations have shown that podoplanin is selectively expressed in lymphatic endothelium as well as lymphangiomas, Kaposi sarcomas, and in a subset of angiosarcomas with probable lymphatic differentiation. Podoplanin has also been shown to be strongly expressed in seminomas, epithelioid mesotheliomas, and hemangioblastomas, and immunostaining for this marker can assist in the diagnosis of these tumors. This article reviews the current information on the applications of podoplanin immunostaining in surgical pathology.     

Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry

 

Aim:

Antigen retrieval (AR) procedures are based on the effect of heating (by either microwave or pressure cooking treatments) on routinely fixed and paraffin embedded tissues. We observed that AR procedures restore the reactivity of endogenous biotin (EB) and report on the distribution of EB following AR in a series of routinely fixed and embedded tissues.  

Methods and results:

Following pressure cooking or microwave treatments, a simple streptavidin–peroxidase staining revealed retrieved endogenous biotin (REB) in normal tissues (such as liver, kidney and adrenal cortex), in oxyphylic cells and in some tumours, especially in carcinomas of the kidney and of the adrenal cortex. In formalin-fixed (but not in alcohol-fixed) tissue sections, the heating procedures caused an intense and finely granular cytoplasmic reaction, following a routine streptavidin-conjugated peroxidase treatment. The staining was prevented by blocking of EB by a sequential avidin–biotin treatment.  

Conclusions:

Retrieval of EB reactivity can cause pitfalls in diagnostic immunohistochemistry but, alternatively, it might also constitute a useful and novel diagnostic marker.     

Myristoyl-CoA:protein N-myristoyltransferase: a novel molecular approach for cancer therapy (Review)

Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. The treatment of colonic cancer remains difficult because of the lack of effective chemotherapeutic agents; therefore it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs resulting in the inhibition of the development and progression of cancer. The current knowledge of the modification of proteins by myristoylation involving myristoyl-CoA:protein N-myristoyltransferase (NMT) is in its infancy. This process is involved in the pathogenesis of cancer. We have reported for the first time in rats treated with azoxymethane that NMT activity was higher in colonic epithelial neoplasms than in normal colonic tissue and that an increase in NMT activity appeared at an early stage in colonic carcinogenesis. Increased NMT activity was also confirmed in human colonic tumors compared to normal tissue. Furthermore, colorectal tumors displayed increased immunohistochemical staining for NMT compared to normal mucosa in the cytoplasm. In addition, gallbladder carcinoma showed moderate to strong cytoplasmic positivity for NMT with increased intensity in the invasive component whereas the normal gallbladder mucosa showed weak to negative cytoplasmic staining for this enzyme. It is conceivable therefore that NMT can be used as a potential marker for the early detection of cancer. Of particular note is the very recent discovery of cytotoxic compounds in the laboratories of the authors which inhibit NMT and may offer a novel approach for the evolution of candidate antineoplastic agents which display greater potencies towards neoplasms than the corresponding normal tissues.     

Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer

Morikawa T, Maeda D, Kume H, Homma Y & Fukayama M
(2010) Histopathology 57, 885–892 Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer Aims: To examine the immunohistochemical expression and function of ribonucleotide reductase M2 subunit (RRM2), a gemcitabine‐related molecule, in bladder cancer. Methods and results: One hundred and seventeen bladder specimens on a tissue microarray were immunostained for RRM2. Positive RRM2 staining was observed in none of 14 examples of non‐neoplastic urothelium, none of four low‐grade urothelial carcinoma (UC), 69 of 83 (83%) high‐grade UC, three of three (100%) squamous cell carcinoma and 12 of 13 (92%) lymph node metastasis of UC. RRM2 overexpression was associated significantly with muscularis propria invasion in UC patients who had undergone radical cystectomy (P = 0.005). Immunohistochemistry for RRM2 was then applied to small biopsy specimens of 15 cystitis with reactive atypia cases and 25 urothelial carcinoma in‐situ (CIS) cases. Positive RRM2 staining was found in one of 15 (6.7%) cystitis with reactive atypia cases and in 24 of 25 (96%) CIS cases. Finally, UM‐UC‐3 bladder cancer cells were transfected with RRM2 siRNAs and cell growth was evaluated. Knockdown of RRM2 protein markedly inhibited cell growth. Conclusions: We have shown frequent overexpression of RRM2 protein and its possible role in bladder cancer. Our results suggest that RRM2 is a novel diagnostic marker and a potential therapeutic target in bladder cancer.     

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis

The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.     

Endophytic malignant transformation within flat adenoma of the colon: A potential diagnostic pitfall

A 74-year-old man was found to have a 1 cm, slightly elevated and flat, red mucosal lesion of the descending colon. An endoscopic biopsy showed a structure characteristic of a tubular adenoma. The surgical specimen revealed an inverted, transmural, solid and cystic lesion. The superficial (intra-mucosal) component of the neoplasm was histologically characteristic of a flat adenoma, showing epithelial dysplasia. However, the contiguous deep component was a well-differentiated adenocarcinoma extending to the serosa and demonstrating the unusual features of a circumscribed lobulated topography and the absence of an inflammatory/desmoplastic stromal reaction. Endophytic malignant transformation within a flat adenoma should be distinguished from conditions of misplaced glandular epithelium such as localized colitis cystica profunda. Complete and full mucosal thickness endoscopic snare removal is indicated in order to assess the degree of epithelial dysplasia and detect endophytic malignant transformation.     

Cathepsin B: a potential prognostic marker for inflammatory breast cancer

Background  

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.     

Trisomy 7: A potential cytogenetic marker of human prostate cancer progression

We used the fluorescence in situ hybridization (FISH) method to show that chromosome 7 trisomy is associated with the progression of human prostate cancer. Thirty-six specimens including 15 primary prostate carcinomas, 16 metastatic lesions, and 5 normal prostate tissues, as well as 2 prostate carcinoma cell lines of different tumorigenic potential, were examined for chromosome 7 aneuplaidy. Our results showed that the androgen-unresponsive tumorigenic cell line PC-3 exhibited a significantly higher ratio of chromosome 7 to total chromosome number than the androgen-responsive nontumorigenic cell line LNCaP (P = 0.001). In prostate specimens, the frequency of trisomy 7 cells was significantly increased (P < 0.05) in the advanced stage tumors (C and D1) but not in the early (6) stage tumors or normal prostatic tissue. Furthermore, metastases showed a higher frequency of trisomy 7 cells than primary tumors (P = 0.005). In 2 patients with paired primary and metastatic tumors, trisomy 7 cells increased from 4-7% in the primary tumors to 42-45% in the metastatic tumor cells in the bone marrow. Therefore, our data suggest that trisomy 7 may be a common feature associated with local and metastatic progression and serve as a novel marker for human prostate cancer progression. Genes Chrom Concer 9:/9-27 (1994). © 1994 Wiley-Liss, Inc.     

Survivin as a diagnostic and therapeutic marker for thyroid cancer

Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.     

miRNA genetic variants: As potential diagnostic biomarkers for oral cancer

MicroRNAs (miRNAs) comprise a novel class of small, non-coding endogenous RNAs that have a role in the plethora of regulatory activities by directing their target mRNAs for degradation or translational repression. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in serious consequences. Detection of miRNA-polymorphisms can potentially improve diagnosis, treatment, prognosis in patients and has extreme implications in the fields of pharmacogenomics and personalization of medicine. The aim of this study is to investigate the association between miR-499 A/G and miR-149 C/T polymorphisms with susceptibility to development of Oral Squamous Cell Carcinoma (OSCC). 200 histopathologically diagnosed and confirmed samples from OSCC patients and 200 control samples from the general population were recruited for the study. All OSCC patients were graded based on their differentiation, and genetic analysis was performed by PCR-RFLP and sequencing. qRT-PCR was carried out to compare the expression of miR-499 and miR-149 in different grades of various stages of OSCC patients concerning to the controls. Further Immunohistochemistry (IHC) was performed to study the target gene of miR-499. The study shows a probable association of miR-499 A/G and miR-149 C/T with susceptibility of OSCC. Random sequencing analysis and Immunohistochemistry contribute to the result that miR-499 A/G increases the susceptibility of OSCC by targeting SOX-6. PCR- Restriction Fragment Length Polymorphism (RFLP) and multivariable logistic analysis revealed that there is a significant association between miR-149 CT + TT and CT and susceptibility of OSCC. Our study suggests that miR-499 A/G and miR-149 C/T polymorphisms may play crucial roles in susceptibility and development of OSCC in Indian population.     

Heart fatty acid binding protein as a potential diagnostic marker for neurodegenerative diseases

The diagnosis of neurodegenerative diseases with dementias requires several different test approaches and often remains uncertain. Using a proteomic approach it was shown in nine patients that heart fatty acid binding protein (H-FABP) might be a biomarker for Creutzfeldt-Jakob disease (CJD). The aim of our study was to evaluate whether H-FABP is a biomarker for the differential diagnosis of dementias. Therefore we measured H-FABP in cerebrospinal fluid (CSF) and serum of patients having CJD, dementia with Lewy-bodies (DLB), Alzheimer's disease (AD) and in non-demented control (NDC) patients. H-FABP levels in CSF and serum of CJD patients are increased compared to non-demented controls. Levels of H-FABP were significantly higher in CJD patients compared to AD and DLB in CSF. However, discrimination between CJD and AD was not possible in serum. Interestingly, highest levels of H-FABP were found in serum of DLB patients. Our results suggest that H-FABP might be a useful biomarker for the differentiation between the dementias examined if levels in CSF and serum are determined in parallel.     

Cyclin A1 and gametogenesis in fertile and infertile patients: a potential new molecular diagnostic marker

BACKGROUND: The study aim was to evaluate cyclin A1 mRNA expression levels as a potential molecular diagnostic parameter in the work-up of testicular tissue from fertile versus infertile patients. METHODS: Cyclin A1 expression was quantified in 55 cryopreserved testicular tissue specimens by fluorescence real-time RT-PCR. A conventional histological work-up was performed concomitantly in all tissue specimens with additional semi-thin sectioning in all cases of non-obstructive azoospermia (n = 12), maturation arrest (n = 17) and Sertoli cell-only syndrome (SCOS; n = 9). RESULTS: The mean (+/- SD) normalized cyclin A1 expression (N(CyclinA1)) was 3.82 +/- 2.23 relative gene expression (RGE) in tissue specimens with normal spermatogenesis, and 0.625 +/- 0.221 RGE in those with maturation arrest at the level of early spermatids. Only minimal N(CyclinA1) was detected in tissue specimens with spermatogonia only or maturation arrest at the level of primary spermatocytes (0.005 +/- 0.008). Cyclin A1 expression was absent in the majority of SCOS specimens (0.002 +/- 0.002). CONCLUSIONS: These investigations suggested that cyclin A1 expression is altered in cases of spermatogenic disorders. Moreover, the level of cyclin A1 mRNA expression correlates with gametogenic disorders and seems well suited for a molecular-diagnostic classification supplementing the histopathological evaluation of spermatogenic disorders.     

Colon cancer-associated DNA mutations: marker selection for the detection of proximal colon cancer.

This study evaluates the potential ability of a specific panel of DNA mutations to identify right-sided colorectal carcinomas (CRCs) that would be missed by a flexible sigmoidoscopy (FS) screening program. This panel could then be applied to stool DNA analysis for noninvasive proximal CRC detection. A series of resected right-sided CRCs from 101 patients who had no left-sided advanced colonic neoplasms distal to the splenic flexure were analyzed. Tumor DNA was isolated from microdissected tumor sections. Deletions in the BAT-26 locus, a marker of microsatellite instability, and mutations at 19 loci spread among the p53, K-ras, and Apc genes were detected following PCR amplification. Mutations were identified in 83% of successfully amplified samples and were variably present in each of the target sites: p53 (42%), Apc (37%), K-ras (28%), and BAT-26 (24%). Mutations were identified across all Dukes stages (CIS/A 6/8 [75%], B 41/51[80%], C 30/32 (94%), and D 6/9 [67%]). Our data suggest that this 20-marker mutation panel may be associated with more than 80% of cancers undetectable by FS. The adjunctive use of stool DNA mutation analysis using this marker panel in FS CRC screening programs may significantly increase the detection of proximal CRC.     

Search of a novel diagnostic marker for allergic diseases by the microarray approach

It is well known that Th2-type immune response is important for the pathogenesis of allergic diseases, such as bronchial asthma, allergic rhinitis, and atopic dermatitis. However, the pathogenesis of allergic diseases is heterogeneous, in that various cells and mediators are involved. If a relevant marker to discriminate the pathogenesis of allergic diseases in each individual could be found, such a marker would be beneficial to carry out personalized therapy for allergic diseases. We have recently found that squamous cell carcinoma antigens 1 and 2, which are now widely used as biomarkers to diagnose squamous cell carcinomas, are downstream molecules of interleukin-4 and interleukin-13, Th2-type cytokines, by the microarray approach. We furthermore found that these molecules are relevant biomarkers for bronchial asthma and atopic dermatitis. It is hoped that the measurement of squamous cell carcinoma antigens will be useful to diagnose allergic patients to apply agents targeting interleukin-4 or interleukin-13 in the future.     

Stem cell factor as a novel diagnostic marker for early malignant germ cells

Carcinoma in situ (CIS) of the testis is the pre-invasive stage of type II testicular germ cell tumours (TGCTs) of adolescents and adults. These tumours are the most frequently diagnosed cancer in Caucasian adolescents and young adults. In dysgenetic gonads, the precursor of type II GCTs can be either CIS or a lesion known as gonadoblastoma (GB). CIS/GB originates from a primordial germ cell (PGC)/gonocyte, ie an embryonic cell. CIS can be cured by local low-dose irradiation, with limited side effects on hormonal function. Therefore, strategies for early diagnosis of CIS are essential. Various markers are informative to diagnose CIS in adult testis by immunohistochemistry, including c-KIT, PLAP, AP-2gamma, NANOG, and POU5F1 (OCT3/4). OCT3/4 is the most informative and consistent in presence and expression level, resulting in intense nuclear staining. In the case of maturational delay of germ cells, frequently present in gonads of individuals at risk for type II (T)GCTs, use of these markers can result in overdiagnosis of malignant germ cells. This demonstrates the need for a more specific diagnostic marker to distinguish malignant germ cells from germ cells showing maturation delay. Here we report the novel finding that immunohistochemical detection of stem cell factor (SCF), the c-KIT ligand, is informative in this context. This was demonstrated in over 400 cases of normal (fetal, neonatal, infantile, and adult) and pathological gonads, as well as TGCT-derived cell lines, specifically in cases of CIS and GB. Both membrane-bound and soluble SCF were expressed, suggestive of an autocrine loop. SCF immunohistochemistry can be a valuable diagnostic tool, in addition to OCT3/4, to screen for precursor lesions of TGCTs, especially in patients with germ cell maturation delay.     

炎症性疾病早期诊断的新指——sTREM-1

髓系细胞表达的触发受体-1(TREM-1)是新近确认的一个与炎症相关的免疫球蛋白超家族成员,表达于中性粒细胞、成熟的单核细胞、巨噬细胞表面.多种细菌性成分能使细胞表面的TREM-1表达增加,后者与Toll样受体协同作用,激发炎症因子的产生.最新的研究发现,感染过程中一种可溶性TREM-1(sTREM-1)可释放进入体液,并且与多种疾病如肺炎、细菌性脑膜炎、炎症性肠病密切相关,成为一种早期诊断炎症性疾病的新指标.     

Cutaneous epithelioid angiosarcoma: A potential diagnostic trap for cytopathologists

We report on the cytologic features of a rare case of cutaneous epithelioid angiosarcoma of the scalp occurring in a 65-yr-old Chinese male. The prominent epithelioid features may cytologically mimic poorly-differentiated carcinoma, malignant melanoma, and even epithelioid sarcoma. Recognition of subtle cytologic features of vasoproliferation, immunohistochemical demonstration of endothelial markers, and ultrastructural examination are necessary before a final conclusion may be drawn. Diagn. Cytopathol. 16:160–167, 1997. © 1997 Wiley-Liss, Inc.     

Role of calpain and caspase system in the regulation of N-myristoyltransferase in human colon cancer (Review)

A number of viral and eukaryotic proteins which undergo a lipophilic modification by the enzyme N-myristoyltransferase (NMT: NMT1 and NMT2) are required for signal transduction and regulatory functions. We reported a higher expression of NMT2 in most of the cases of cancerous tissues compared to normal tissues by Western blot analysis. Furthermore, protein-protein interaction of NMTs revealed that m-calpain interacts with NMT1 while caspase-3 interacts with NMT2. Our findings provide the first evidence of higher expression of NMT2 in human colorectal adenocarcinomas and the interaction of both forms of NMT with various signaling molecules. In this review, we summarize the recent findings on NMT2 in human colon cancer in our laboratory.