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Biomedical subjects

M Salto-Tellez

Publications and source records attributed to M Salto-Tellez.

At least 19 recordsLinked to original sources
PubMed2006

RUNX3 protein is overexpressed in human basal cell carcinomas.

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

Blotting, Western↗
PubMed2006

Metastasis-associated protein S100A4--a potential prognostic marker for colorectal cancer.

BACKGROUND AND OBJECTIVES: Expression of S100A4, a small calcium-binding protein, in breast, oesophagus and gall bladder cancers is shown to be associated with adverse clinical outcome. We retrospectively examined the correlation of S100A4 expression and outcome in patients with colorectal cancer. METHODS: Tissue sections from 54 patients with Dukes B, C and D cancers operated on between 1995 and 1998 were stained with anti-S100A4 antibody. The S100A4 expression profile was correlated to the clinico-pathological details. RESULTS: There were 31 males and 23 females (mean age 65.94 years +/- 12.29). Dukes stage, >4 positive lymph node status and S100A4 expression were significantly associated with poorer survival. The 3 years survival of patients whose tumour stained positive for S100A4 was 62.85% compared to 93.75% for those stained negative (P < 0.012). In patients with <4 involved nodes, S100A4 expression led to poorer survival (57 months vs. 74 months; P < 0.0052). Within a particular Dukes stage, S100A4 expression was associated with poorer outcome. The 5 years survival of Dukes B patients whose tumour stained negative for S100A4 was 92% compared to 54.6% for those with positive tumours. CONCLUSION: Our results suggest that S100A4 expression is associated with adverse clinical outcome. Inclusion of S100A4 expression status may enhance our accuracy to prognosticate in patients with colorectal cancer.

Adult↗
PubMed2005

Metastatic testicular carcinoma from the colon with clinical, immunophenotypical, and molecular characterization: report of a case.

We report a case of testicular metastasis from a colonic adenocarcinoma. The presentation of testicular metastasis, diagnosis, management, and possible modes of spread are reported. In addition to conventional investigations and histopathologic techniques, a molecular study of the testicular metastasis and colon primary, using microsatellite analysis, was performed to confirm the primary origin. Its potential uses are discussed.

Aged↗
PubMed2005

Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1.

Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Apoptosis↗
PubMed2005

Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia.

Lee S-C, Guo J-Y, Lim R, Soo R, Koay E, Salto-Tellez M, Leong A, Goh B-C. Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia. Hereditary non-polyposis colorectal cancer (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form of hereditary colorectal cancer (CRC), but data in Asians are sparse. We sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients diagnosed below age 40, and/or with multiple primary cancers or familial cancer clustering suggestive of HNPCC, and correlated deleterious mutations with clinical and tumour features. Forty-six Chinese, Malay and Indian kindreds participated. Of the 153 cancers reported in the 46 kindreds, stomach (14%) and urogenital cancers (13%) were the most common extracolonic cancers, whereas endometrial cancer comprised only 7%. Eleven different MLH1 and 12 MSH2 mutations were identified, including nine novel and four recurring mutations in the Chinese. One Indian was a compound heterozygote for an MLH1 and MSH2 mutation. The MLH1/MSH2 mutation data in the Malays and the Indians represents the first in these ethnic groups. Factors strongly associated with deleterious mutations were the Amsterdam criteria, family history of stomach or multiple primary cancers, and MSI-high tumours, whereas family history of endometrial cancer and young cancer age alone correlated poorly. Distinct clinical and molecular characteristics were identified among Asian HNPCC kindreds and may have important clinical implications.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Discordant quantitative detection of putative biomarkers in nodal micrometastases of colorectal cancer: biological and clinical implications.

AIMS: Nodal expression of the carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), and guanylyl cyclase C (GCC) genes was measured in tandem in patients with colorectal cancer (CRC) to assess whether there would be sufficient agreement between these markers in their ability to detect micrometastasis to qualify one of them as a universal marker, and whether frozen and paraffin wax embedded tissues would yield similar results. METHODS: One hundred and seventy five frozen lymph nodes (FT) and 158 formalin fixed, paraffin wax embedded lymph nodes (PET) from 28 CRC cases were analysed using gene specific quantitative real time polymerase chain reaction, carried out on the LightCycler system with SYBR Green chemistry. RESULTS: There was significant disparity in positive detection of the three biomarkers in FT versus PET, with notable agreement achieved only for CEA (66.6%) in FT versus PET in Dukes' B disease, and between CK20 and GCC (44.6%) in FT, also in Dukes' B disease. One patient with full concordance in all three tumour markers with both tissue types suffered a relapse and died within two years of follow up. CONCLUSIONS: There was considerable discordance in the positive detection of the three tumour markers in both tissue types (FT versus PET). This brings into question whether using a single tumour marker to detect micrometastasis in one tissue type (FT or PET) is adequately representative, and challenges the concept of universal markers for molecular CRC metastatic detection. Multiple tumour markers would predict more accurately the metastatic potential of Dukes' B CRCs.

Adenocarcinoma↗
PubMed2004

Molecular diagnostic cytopathology: definitions, scope and clinical utility.

Molecular diagnosis is the application of molecular biology techniques and knowledge of the molecular mechanisms of disease to diagnosis, prognostication and treatment of diseases. Although it is not widely used in routine molecular cytological practice, some examples are presented here of the application of molecular techniques to the routine cytopathological diagnosis of solid tumours and lymphoreticular malignancies. The term 'molecular diagnostic cytopathology' is proposed to define the application of molecular diagnosis to cytopathology, and the challenges of the introduction of molecular diagnosis into routine diagnostic histopathology and cytopathology are discussed. Finally, the importance of a combined morphological, immunophenotypic and molecular approach to maintain the diagnostic pathologist at the heart of the clinical decision-making process is emphasized.

Cytodiagnosis↗
PubMed2004

Lymphocytic gastritis-like T cell lymphoma: molecular evidence of an unusual recurrence.

This report describes a patient with a gastric biopsy specimen showing histomorphological and immunohistochemical appearances indistinguishable from those usually present in lymphocytic gastritis, a rare condition of unknown aetiology with a distinctive phenotype. The patient had a history of a biopsy confirmed T cell non-Hodgkin lymphoma at two anatomical sites (bladder and stomach), which was subsequently treated. Molecular analysis of the T cell receptor (TCR) gamma chain gene rearrangements showed a distinct monoclonal T cell population in the bladder and gastric biopsies. The same analysis in the lymphocytic gastritis-like biopsy sample showed a monoclonal population with identical base pair size to that identified in the other specimens. This report highlights the importance of TCR gene rearrangement analysis in the diagnosis of unusual gastric inflammation, and the use of capillary electrophoresis based polymerase chain reaction in the follow up of lymphoproliferative disorders.

Antigens, CD↗
PubMed2003

Sequence confirmation of the EWS-WT1 fusion gene transcript in the peritoneal effusion of a patient with desmoplastic small round cell tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated neoplasm. The prognosis is poor, even if therapy is instituted promptly, and thus it is important to differentiate it from other histologically and cytologically similar-looking malignancies of the young adult. We present a case of DSRCT in a 17-yr-old male with disseminated peritoneal disease and peritoneal effusion. The cytology sample showed a malignant small round cell tumor, the classical cytological features of DSRCT, and immunohistochemistry performed in the prepared cell block exhibited an antibody expression profile in keeping with DSRCT. Further material from the effusion was prepared for RNA extraction, following which a reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing of the t(11;22)(p13;q11 or q12) were carried out. The result showed the presence of the reciprocal translocation and thus confirmed the diagnosis of DSRCT. This case shows how molecular techniques (including sequencing) can be applied to cytology in clarifying and confirming certain difficult diagnosis of undifferentiated neoplasms, DSRCT in this particular case.

Adolescent↗
PubMed2003

Intrinsic variability in the detection of micrometastases in lymph nodes for re-staging of colorectal cancer. effect of individual markers and tissue samples.

In this study, we investigated whether (a) carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20) and guanylyl cyclase C (GCC) are clinically useful markers for the molecular detection of submicroscopic metastases in colorectal cancer (CRC) and (b) whether overexpression of CEA, CK-20 and GCC can be reliably detected in formalin-fixed, paraffin-embedded tissues as well as frozen lymph nodes. We studied 175 frozen lymph nodes and 158 formalin-fixed, paraffin-embedded lymph nodes from 28 cases of CRC. CEA or CK-20 or GCC-specific polymerase chain reaction (PCR) was carried out on mRNA transcripts extracted from the nodal tissues. Ten out of 11 Dukes' B CRC cases had detectable CEA and CK-20 while 6 out of 11 Dukes' B CRC cases had detectable GCC. In general, the difference of re-staged cases when comparing frozen and paraffin-embedded samples was marked; the only statistically significant correlation between frozen and paraffin tissue was for the CEA marker. Our results indicated a high incidence (>50%) of detecting micrometastases in histologically-negative lymph nodes at the molecular level.

Adult↗
PubMed2003

Immunocytochemistry versus molecular fingerprinting of metastases.

Examination of cytological samples of cancer to suggest a possible primary site of origin is one of the commonest and most difficult tasks of diagnostic cytopathologists. Currently, both cytomorphology and immunocytochemistry are the main approaches to this diagnostic dilemma. We report the application of microsatellite analysis in cytological samples in a patient with a primary colonic tumour and two subsequent lung nodules, which were suspected on CT scans of the chest, and compared the findings with those obtained with conventional immunocytochemistry. The molecular results were in agreement with the radiological impression and conflicted with the immunocytochemistry. We conclude that immunocytochemical and molecular biology approaches to the diagnosis of tumours may give rise to contradictory results.

Adenocarcinoma↗
PubMed2003

Cervical cytology: an audit in a Singapore teaching hospital.

OBJECTIVES: To describe the cervical cytology diagnoses and cyto-histological correlation in the Department of Pathology, National University of Singapore in 1997 and to compare the data with international figures. METHODS: A database search of all cervical cytology cases diagnosed in the department in 1997 as well as follow-up biopsies was carried out. The data was then critically analysed. RESULTS: 10,207 cases were reviewed. 96% of the cases had a diagnosis of "negative". Under 1% of cases were labelled as "inadequate". "Atypia" was diagnosed in 1% and dysplasia and/or malignancy was diagnosed in 1%. These figures correlate well with international data. Of the dysplasia cases, 78% were followed by biopsy. Of the high-grade dysplasia cases that were biopsied, 97% of the biopsy diagnoses were within the acceptable concordance range with the cytology diagnoses and in only 3% was there a significant discrepancy. Of the cases diagnosed as atypia, 39% were subsequently biopsied at the same institution as the next procedure and only one showed high grade dysplasia. A total of six cases showed a significant discrepancy between the cervical cytology result and the subsequent biopsy diagnosis and these were reviewed to elucidate the reasons for the discrepancies. CONCLUSION: The cervical cytology service is of a high diagnostic standard. A subset of patients is probably being prematurely biopsied and may benefit from having a repeat smear instead. Specific clinical protocols regarding subsequent therapy following cytology results and closer cyto-histological correlation are two main areas where the cytology service can be improved.

Biopsy↗