A BCR/ABL‐negative chronic myeloid leukemia (CML) with t(12;14)(p12;q11‐13) as the sole chromosomal abnormality was investigated by fluorescence in situ hybridization (FISH), which disclosed a cryptic insertion of ETV6 (previously called TEL), located at 12p12, into ABL at chromosome band 9q34. ETV6/ABL fusion was confirmed by RT‐PCR, revealing that the first five exons of ETV6 were fused in frame with ABL at exon 2. Wild‐type ETV6 was expressed, in accordance with the FISH results showing no deletion of the second ETV6 allele. ETV6/ABL chimeric transcripts have previously been reported in acute leukemias, but never before in CML. The present case suggests that ETV6/ABL positivity may constitute a new genetic subgroup of BCR‐negative CML. Genes Chromosomes Cancer 20:299‐304, 1997. © 1997 Wiley‐Liss, Inc.

Celiac disease (CD) is identified by histopathologic changes in the small intestine which normalize during a gluten-free diet. The histopathologic assessment of duodenal biopsies is usually routine but can be difficult. This study investigated gene expression profiling as a diagnostic tool. A total of 109 genes were selected to reflect alterations in crypt-villi architecture, inflammatory response, and intestinal permeability and were examined for differential expression in normal mucosa compared with CD mucosa in pediatric patients. Biopsies were classified using discriminant analysis of gene expression. Fifty genes were differentially expressed, of which eight (APOC3, CYP3A4, OCLN, MAD2L1, MKI67, CXCL11, IL17A, and CTLA4) discriminated normal mucosa from CD mucosa without classification errors using leave-one-out cross-validation (n ϭ 39) and identified the degree of mucosal damage. Validation using an independent set of biopsies (n ϭ 27) resulted in four discrepant cases. Biopsies from two of these cases showed a patchy distribution of lesions, indicating that discriminant analysis based on single biopsies failed to identify CD mucosa. In the other two cases, serology support class according to discriminant analysis and histologic specimens were judged suboptimal but assessable. Gene expression profiling shows promise as a diagnostic tool and for follow-up of CD, but further evaluation is needed. (Pediatr Res 69: 530-537, 2011) C eliac disease (CD) is an inflammatory condition of the small intestine with a diverse range of symptoms (1), and a prevalence of approximately 1% in Western European populations (2). CD is triggered by gliadin peptides derived from gluten-containing cereals, and the inflamed small intestinal mucosa is characterized by villous atrophy, crypt hyperplasia, and infiltration of lymphocytes in the epithelium (1). In addition, patients with CD have increased permeability over the epithelial layer of the small intestine, and an altered structure of the tight junction has been demonstrated in children with CD (3).A positive serological test for antibodies against tissue transglutaminase and/or gliadin may indicate CD (4). However, a histopathologic assessment (HA) of small intestinal biopsies regarding abnormalities characteristic of CD is required to establish a diagnosis (5,6). Diagnostic criteria also require that the patient should have a clinical remission when on a strict gluten-free diet (GFD). The mucosal damage is often graded histologically, using such established measures as the modified Marsh scale (7). The interobserver reproducibility between pathologists assessing the same small intestinal biopsy specimens shows fair to substantial agreement (8,9), with most of the disagreements found in Marsh 1-3B lesions (8) and with some of the interpathologist assessments transgressing the boundary between normal mucosa and CD mucosa (8).Gene expression profiling shows a potential as a robust test for classification purposes, with a high interlaboratory reproducibility (10,11). A ...

Objective: Meningioma-associated protein (MAC30) is overexpressed in several types of cancers, but its therapeutic implication in the patients has not been studied. We examined the relationship of MAC30 with clinicopathological and biological factors in rectal cancer patients with or without radiotherapy (RT). Methods: MAC30 was immunohistochemically examined in 75 distant and 91 adjacent normal mucosa specimens, 132 primary tumours and 39 lymph node metastases from rectal cancer patients participating in a clinical trial of preoperative RT. Results: In the RT group, MAC30 was or tended to be positively correlated with infiltrated growth pattern (p = 0.02), PRL (phosphatase of regenerating liver, p = 0.01) and Ki-67 expression (p = 0.06). MAC30 at the invasive margin of the metastasis was related to poor survival (p = 0.02) in the whole group of patients. MAC30 in primary tumours was not related to recurrence and survival in the non-RT or RT group. Conclusions:MAC30 expression in metastasis was an indicator for poor survival. After RT, MAC30 seemed to be more related to aggressive morphological and biological factors; however, we did not find direct evidence that MAC30 expression was related to the outcome of patients with or without RT.

Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.

The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age ≥70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged <70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged ≥80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged <70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged ≥80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged ≥80 years had a higher 30-day mortality than younger patients (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.6–4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20–4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.05–2.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21–3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged ≥80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.