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Journal of clinical pathology [journal]
- Importance of carcinoma-associated fibroblast-derived proteins in clinical oncology. [REVIEW]
- J Clin Pathol 2014 Aug 18.
Carcinoma-associated fibroblast (CAF) as prominent cell type of the tumour microenvironment has complex interaction with both the cancer cells and other non-neoplastic surrounding cells. The CAF-derived regulators and extracellular matrix proteins can support cancer progression by providing a protective microenvironment for the cancer cells via reduction of chemotherapy sensitivity. On the other hand, these proteins may act as powerful prognostic markers as well as potential targets of anticancer therapy. In this review, we summarise the clinical importance of the major CAF-derived signals influencing tumour behaviour and determining the outcome of chemotherapy.
- CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Aug 12.
Perineural invasion and expression of CXCR4 is characteristic of adenoid cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC, identify its association with perineural invasion and investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model.Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo.CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour in the animal model and in the tumour of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model.CXCR4 is associated with perineural invasion in ACC. AMD3100, which can effectively diminish perineural invasion of ACC, may have an adjuvant role in the management of ACC.
- Predictive markers of radiotherapy-induced rectal cancer regression. [REVIEW]
- J Clin Pathol 2014 Aug 12.
Patients with locally advanced rectal cancer receive preoperative radiotherapy to reduce the probability of recurrence and to possibly improve overall survival. However, this appears dependent on the extent of histological tumour regression seen in the resected bowel, which can be highly variable between individuals. No predictive marker that can stratify patient management in this regard is currently available. Experimental data implicates a variety of factors that are involved in the DNA damage response following radiation injury, tumour tissue oxygenation, autoimmune antitumour response triggered by radiotherapy and in the pathogenesis of colorectal cancer, as potential indicators of radiation sensitivity. These details are presented in this review, which may serve as targets for clinical validation studies aiming to find predictors of radiotherapy response in rectal cancer.
- Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Aug 12.
Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations in IGF1R copy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases.IGF1R gene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, including EGFR and KRAS mutational status and patient survival.IGF1R gene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibited IGF1R gene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation between IGF1R gene copy number and protein expression (r=0.2, p<0.05). Alterations of IGF1R gene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). High IGF1R gene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade, EGFR or KRAS mutational status or overall survival.High IGF1R gene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant.
- p70 Ribosomal protein S6 kinase (Rps6kb1): an update. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Aug 6.
The Rps6kb1 gene encodes the 70 kDa ribosomal protein S6 kinase (p70S6K), which is a serine/threonine kinase regulated by phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway. p70S6K plays a crucial role in controlling cell cycle, growth and survival. The PI3K/mTOR signalling pathway is one of the major mechanisms for controlling cell survival, proliferation and metabolism and is the central regulator of translation of some components of protein synthesis system. Upon activation, this kinase phosphorylates S6 protein of ribosomal subunit 40S resulting in selective translation of unique family of mRNAs that contain oligopyrimidine tract on 5' transcriptional site (5'TOP). 5'TOP mRNAs are coding the components of translational apparatus including ribosomal proteins and elongation factors. Due to the role of p70S6K in protein synthesis and also its involvement in a variety of human diseases ranging from diabetes and obesity to cancer, p70S6K is now being considered as a new therapeutic target for drug development. Furthermore, p70S6K acts as a biomarker for response to immunosuppressant as well as anticancer effects of inhibitors of the mTOR. Because of the narrow therapeutic index of mTOR inhibitors, drug monitoring is essential, and this is usually done by measuring blood drug levels, therapeutic response and drug-induced adverse effects. Recent studies have suggested that plasma p70S6K is a reliable index for the monitoring of patient response to mTOR inhibitors. Therefore, a better understanding of p70S6K and its role in various pathological conditions could enable the development of strategies to aid diagnosis, prognosis and treatment schedules.
- α-Methylacyl-CoA racemase (AMACR) serves as a prognostic biomarker for the early recurrence/metastasis of HCC. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Aug 4.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is still lacking effective prognostic biomarkers so far. Previous results of the iTRAQ-based quantitative proteomics study (iTRAQ-2DLC-MS/MS) have shown that α-methylacyl-CoA racemase (AMACR) might be a promising prognostic biomarker for the early recurrence/metastasis of hepatocellular carcinoma (HCC). Here a large-scale cohort clinical study was performed to evaluate its prognostic potential.HCC samples from patients (n=158) were used for the construction of tissue microarray. The expression level of AMACR was determined by immunohistochemical staining. A large-scale cohort clinical study between the expression of AMACR and some major clinical parameter has been performed to assess the prognostic potential of AMACR for the early recurrence/metastasis of HCC.Some important clinical parameters such as α-fetoprotein, tumour numbers, dissemination to regional lymph nodes, tumour capsule and portal vein tumour thrombosis are significantly associated with the low expression of AMACR. The expression of AMACR was an independent factor for the survival of patients with HCC. The median survival time was 17 months in the low-expression group compared with 45 months in the high-expression group.This study reveals that the AMACR might be a potential prognostic marker for predicting early recurrence/metastasis of HCC after hepatectomy.
- Some observations on pyloric gland adenoma: an uncommon and long ignored entity! [REVIEW]
- J Clin Pathol 2014 Aug 4.
Pyloric gland adenomas (PGAs) are uncommon to rare and are found mostly in the stomach but in a number of other anatomical sites as well. They were recognised years ago by European and Japanese colleagues whereas North American pathologists learned to diagnose them more recently. They are associated with conditions that result in pyloric metaplasia, the prototype of which is autoimmune gastritis. Since the latter is more common in women and men, gastric PGA has a striking female predominance. There appear to be differences in the distribution of PGA in various populations. Herein we review PGA and note similarities and differences in their distribution in our institutions in Germany and the USA and review their morphological appearance, immunolabelling profile, and preliminary genetic data on these unusual lesions.
- The surgeon's perspective on oesophageal disease, and what it means to pathologists. [EDITORIAL]
- J Clin Pathol 2014 Aug 4.
- Toker cells of the nipple are commonly associated with underlying sebaceous glands but not with lactiferous ducts. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Aug 1.
Toker cells are clear cells present in the squamous epithelium of the nipple of some women. In contrast to squamous epithelium, they are cytokeratin 7 (CK7) positive. The origin of these cells is not completely understood. It has been suggested that they may represent abortive glands or migratory ductal cells; and may be precursors of Paget's disease of the nipple. Our aim was to investigate the incidence and distribution of Toker cells and their relationship with lactiferous ducts.We examined nipple sections from 100 consecutive mastectomies performed at Charing Cross hospital. New sections were stained for CK7 using the immunoperoxidase technique.Toker cells were identified in 11 cases. They were always clustered within the squamous epithelium superficial to sebaceous glands with no relationship with lactiferous ducts. Two cases in the study had Paget's disease and these were not associated with underlying sebaceous glands.This study suggests that Toker cells are more likely to be developmentally related to sebaceous glands rather than lactiferous ducts. This raises doubts about the presence of a relationship between Toker cells and the common forms of Paget's disease, as the latter are commonly seen in association with ductal carcinoma in situ (DCIS) involving underlying lactiferous ducts. Toker cells, however, may be related to a less common form of Paget's disease which is not associated with underlying DCIS.