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J R Jass

Publications and source records attributed to J R Jass.

At least 91 records · Page 5Linked to original sources
PubMed1998

Accumulated clonal genetic alterations in familial and sporadic colorectal carcinomas with widespread instability in microsatellite sequences.

A subset of hereditary and sporadic colorectal carcinomas is defined by microsatellite instability (MSI), but the spectra of gene mutations have not been characterized extensively. Thirty-nine hereditary nonpolyposis colorectal cancer syndrome carcinomas (HNPCCa) and 57 sporadic right-sided colonic carcinomas (SRSCCa) were evaluated. Of HNPCCa, 95% (37/39) were MSI-positive as contrasted with 31% (18/57) of SRSCCa (P < 0.000001), but instability tended to be more widespread in SRSCCa (P = 0.08). Absence of nuclear hMSH2 mismatch repair gene product by immunohistochemistry was associated with germline hMSH2 mutation (P = 0.0007). The prevalence of K-ras proto-oncogene mutations was similar in HNPCCa and SRSCCa (30% (11/37) and 30% (16/54)), but no HNPCCa from patients with germline hMSH2 mutation had codon 13 mutation (P = 0.02), and two other HNPCCa had multiple K-ras mutations attributable to subclones. 18q allelic deletion and p53 gene product overexpression were inversely related to MSI (P = 0.0004 and P = 0.0001, respectively). Frameshift mutation of the transforming growth factor beta type II receptor gene was frequent in all MSI-positive cancers (85%, 46/54), but mutation of the E2F-4 transcription factor gene was more common in HNPCCa of patients with germline hMSH2 mutation than in those with germline bMLH1 mutation (100% (8/8) versus 40% (2/5), P = 0.04), and mutation of the Bax proapoptotic gene was more frequent in HNPCCa than in MSI-positive SRSCCa (55% (17/31) versus 13% (2/15), P = 0.01). The most common combination of mutations occurred in only 23% (8/35) of evaluable MSI-positive cancers. Our findings suggest that the accumulation of specific genetic alterations in MSI-positive colorectal cancers is markedly heterogeneous, because the occurrence of some mutations (eg, ras, E2F-4, and Bax genes), but not others (eg, transforming growth factor beta type II receptor gene), depends on the underlying basis of the mismatch repair deficiency. This genetic heterogeneity may contribute to the heterogeneous clinical and pathological features of MSI-positive cancers.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Immunoperoxidase staining for cytokeratins 8 and 18 is very sensitive for detection of occult node metastasis of colorectal cancer: a comparison with genetic analysis of K-ras.

AIMS: Recent reports suggest that genetic examination of K-ras or p53 mutation is more sensitive for the detection of occult lymph node metastasis in colorectal carcinomas than conventional examination by haematoxylin and eosin (H & E) staining or immunohistochemistry for gene products. The aim of this study was, first, to define the microscopic characteristics of metastatic cancer cells in lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8 and 18, and, second, to compare the detection rate of occult lymph node metastasis for immunohistochemical vs genetic methods. METHODS AND RESULTS: K-ras mutations were first examined in primary tumours of seven cases which showed distant metastasis or local recurrence within 5 years of the initial surgery in spite of the original reporting of no lymph node metastasis by routine H & E staining. K-ras mutations were positive in three cases in primary tumours and lymph nodes, and the remaining four primary tumours were negative for p53 mutation as well as K-ras mutation. Therefore, genetic analysis of occult lymph node metastasis was uninformative, but occult metastasis was detected by cytokeratin staining in two of these four cases. Comparative study of cytokeratin-positive cells was performed on each of the 43 lymph nodes from three cases with K-ras mutations. Cancer cells were detected in 28 of the 43 lymph nodes (65.1%) by cytokeratin staining and in 10 of the 43 corresponding lymph nodes (23.3%) by genetic analysis. Artefactual contamination by cancer cells was present in eight of the 28 cytokeratin positive lymph nodes, and three of the eight nodes were genetically positive. CONCLUSIONS: This study suggests that cytokeratin immunohistochemistry is more sensitive and specific for the detection of occult lymph node metastasis than genetic diagnosis by K-ras mutation in cases with genetic alterations as well as in cases without them.

Aged↗
PubMed1998

Diagnosis of hereditary non-polyposis colorectal cancer.

The term hereditary non-polyposis colorectal cancer (HNPCC) was introduced initially to encompass autosomal dominant syndromes predisposing to colorectal cancer other than the polyposes. The term is a poor descriptor and is often applied to families on the basis of inadequate information. It is suggested that 'hereditary mismatch repair deficiency syndrome' (HMRDS) should replace the term HNPCC for describing the specific autosomal dominant condition which predisposes to cancer displaying the mutator phenotype. Population-based studies have shown that HMRDS probably accounts for no more than 2% of bowel cancer. A working diagnosis of HMRDS can be made on the basis of clinical, pathological and molecular characteristics. The histopathologist has an important role to play in the recognition and diagnosis of HMRDS. The characteristic morphology of colorectal cancer in HMRDS is reviewed and the diagnostic utility of 'field changes' and adenomas is discussed critically.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1998

Diagnostic value of p53 immunohistochemistry in Barrett's esophagus: an endoscopic study.

The aim of this study was to establish the diagnostic utility of p53 immunohistochemistry in Barrett's esophagus. Three pathologists reviewed endoscopic biopsy specimens and one surgical specimen derived from 102 subjects in a prospective follow-up series. Dysplasia was graded as negative, indefinite, low grade and high grade. p53 staining was assessed as negative, weak or patchy and strong. Kappa coefficients for interobserver agreement for the three combinations of observer pairs were moderate to substantial (0.48, 0.55 and 0.68) for dysplasia and substantial to near perfect (0.77, 0.82 and 0.89) for p53 immunostaining. In the consensus grading achieved for dysplasia, strong p53 staining was recorded in 0/79 samples that were negative or indefinite for dysplasia, 5/15 (33%) examples of low grade dysplasia and 7/8 (87%) examples of high grade dysplasia. Non-dysplastic p53 positive glands were seen in specimens from two subjects harbouring dysplasia or cancer elsewhere. Two p53 positive specimens were, upon review and discussion, re-assigned from low- to high-grade dysplasia. It is concluded that p53 immunohistochemistry facilitates the interpretation of Barrett's epithelium but need only be employed to confirm a suspected diagnosis of dysplasia and assist with the distinction between low- and high-grade dysplasia.

Barrett Esophagus↗
PubMed1998

Intestinal metaplasia subtypes and Helicobacter pylori infection: a comparison of ethnic groups in New Zealand.

Gastric cancer is two to four-fold more common in Maori and Pacific Island ethnic groups compared with Europeans. This study aimed to determine if intestinal metaplasia was more common in these ethnic groups. Patients attending for endoscopy for dyspepsia had six biopsies to determine the presence of Helicobacter pylori by at least two of the following tests: rapid urease test, 13C urea breath test, culture of histology and the presence, extent and subtypes of intestinal metaplasia. Biopsies were taken from 158 patients: Europeans (42%), Maori (23%), Pacific Islanders (35%). Helicobacter pylori and intestinal metaplasia were detected in 88 and 60% of Maori/Pacific Island patients, respectively, and 47 and 29% of Europeans, respectively. Type I intestinal metaplasia was detected in 43% of all patients, type II (26%) and type III (7.0%). The mean age of Maori/Pacific Island patients with intestinal metaplasia and type III intestinal metaplasia was 53 and 51 years respectively, compared with Europeans aged 65 and 72 years. Univariate analysis showed that intestinal metaplasia was associated with ethnicity and H. pylori (P < 0.001) but not age, smoking, endoscopic diagnosis or gender. Intestinal metaplasia is more common and occurs at an earlier age in Maori and Pacific Island patients.

Adult↗
PubMed1998

Morphology of sporadic colorectal cancer with DNA replication errors.

BACKGROUND: Up to 15% of colorectal cancers are characterised by DNA microsatellite instability (MIN), shown by the presence of DNA replication errors (RERs). AIMS: To identify pathological features that are discriminating for colorectal cancer (CRC) showing extensive MIN. SUBJECTS: A prospective series of 303 patients with CRC and no family history of either familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. METHODS: DNA was extracted from fresh tissue samples and the presence of MIN was studied at nine loci that included TGF beta RII, IGFIIR, and BAX. The 61 cases showing RERs were compared with 63 RER negative cases with respect to a comprehensive set of clinical and pathological variables. Predictive utility of the variables was tested by decision tree analysis. RESULTS: Twenty seven patients with CRC showed extensive RERs (three loci or more) (RER+) and 34 had limited RERs only (28 = one locus; 6 = two loci) (RER+/-), yielding a bimodal distribution. RER+ cancers differed from RER- and RER+/-) cases. Tumour type (adenocarcinoma, mucinous carcinoma, and undifferentiated carcinoma) (p = 0.001), tumour infiltrating lymphocytes (p = 0.001), and anatomical site (p = 0.001) were the most significant of the discriminating variables. Algorithms developed by decision tree analysis allowed cases to be assigned to RER+ versus RER- and +/- status with a global sensitivity of 81.5%, specificity of 96%, and overall accuracy of 93%. CONCLUSIONS: Pathological examination of CRC allows assignment of RER+ status; assignment is specific and relatively sensitive. Conversely RER- and RER+/- CRC are indistinguishable.

Adenocarcinoma↗
PubMed1998

Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.

BACKGROUND: Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated. AIMS: To determine the frequency of K-ras mutation in serrated adenoma. METHODS: The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ. CONCLUSIONS: K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.

Adenoma↗
PubMed1998

Loss of heterozygosity and loss of expression of the DCC gene in gastric cancer.

AIM: To investigate the role of DCC gene inactivation in the development and progression of gastric cancer. METHODS: Loss of heterozygosity and loss of expression of the DCC gene was studied in 51 surgical specimens of gastric cancer using detection based on polymerase chain reaction. RESULTS: Loss of heterozygosity was found in 35.3% (18 of 51) of specimens and was detected more often in stage III and IV (50%) than in stage I and II cancers (14.3%) (p < 0.05). Occurrence of loss of heterozygosity was not correlated with histological type, tumour size, depth of invasion, or lymph node metastasis. Loss of expression was found in 49% of cases (25 of 51). Loss of expression was not significantly correlated with any clinicopathological variable. CONCLUSIONS: Loss of heterozygosity and loss of expression of the DCC gene are often encountered in gastric cancer. Loss of heterozygosity of the DCC gene is a late event and associated with malignant progression.

Gene Expression↗
PubMed1997

Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in "node-negative" colorectal cancer.

There is controversy about the prognostic significance of occult lymph node metastases detected by immunohistochemistry with the anti-cytokeratin antibody CAM 5.2. The aim of this study was to characterize occult lymph node metastases in colorectal carcinomas that might be associated with a higher risk of recurrence. Three hundred fifty-eight lymph nodes from 10 recurrent and 9 nonrecurrent cases of colorectal carcinoma were examined. All these patients had been reported originally as having no lymph node metastases by routine hematoxylin and eosin staining. Three 10-micron sections or ten 3-micron sections (30-micron total thickness) from each lymph node were stained with CAM 5.2 and examined for the presence of occult lymph node metastases. Occult metastases were detected in 67 of 175 lymph nodes from the recurrent cases, and in 23 of 183 lymph nodes from the nonrecurrent cases. The frequency of positive nodes was significantly higher in the recurrent cases. The recurrent cases had metastases in nodes more distant from the main tumor than did the nonrecurrent cases. Detection of occult lymph node metastases with cytokeratin immunohistochemistry may make it possible to identify patients with a higher risk of recurrence after the removal of a primary colorectal tumor.

Adult↗
PubMed1997

Future role of the pathologist in reporting colorectal cancer.

A pathology report on a surgical specimen of colorectal cancer has prognostic implications and is assuming increasing importance in relation to decisions regarding postoperative adjuvant therapy. The classic pathologic report is a static description of the extent of spread within the surgical specimen. The clinician, on the other hand, needs to know how far the tumor has spread in the patient. For the radiotherapist the report on rectal cancer must include a detailed account of anatomic location and spread, including relations to peritoneum and extent of mesorectal involvement. The oncologist aims to improve survival of patients undergoing "curative" surgery. Untreated, a subset of such patients die of metastatic disease, occult hepatic metastases being present at the time of surgery. An estimate of the risk of micrometastatic disease requires a prognostic classification utilizing independent pathobiologic variables. Reporting of colorectal cancer needs to become more closely tailored to clinical endpoints relevant to therapeutic decision-making. This paper looks critically at current practice and future directions.

Colorectal Neoplasms↗
PubMed1997

Correlative histochemical study providing evidence for the dual nature of human colorectal cancer mucin.

Luminal secretions within colorectal cancers have been assumed to be the counterpart of normal goblet cell mucin. The aim of this study was to establish whether secretory material within colorectal cancers may in fact be traced to different lineages: goblet cells and columnar cells. The distribution of the apomucins MUC1 and MUC2, non-O-acetylated sialic acid and the carbohydrate structures sialosyl Tn, Tn, Lewis(x), sialosyl Lewis(x) and Lewis(y) was studied in normal colorectal mucosa and colorectal cancer specimens using standard histochemical techniques. Unmasking of MUC1 and MUC2 was achieved using periodic acid and saponification-neuraminidase-periodic acid pretreatment respectively. Within normal and malignant epithelium, correlations and/or co-localization could be demonstrated for goblet cells with MUC2, non-O-acetylated sialic acid, sialosyl Tn, Tn (Golgi region) and sialosyl Lewis(x), and for columnar cells with MUC1, Lewis(x), sialosyl Le(x), Tn (cytoplasm) and Lewis(y) (UEA-1). The goblet cell spectrum was associated with mucin-like (type I) luminal secretions within cancers, whereas the columnar cell spectrum characterized non-mucin-like (type II) secretions and intracytoplasmic lumina. These data indicate that colorectal cancer mucin can be broadly separated into two types: secretory mucin linked to cells of goblet lineage and up-regulated membrane-associated mucin of presumed columnar cell origin.

Biomarkers, Tumor↗
PubMed1997

Failure to detect colonic mucosal hyperproliferation in mutation positive members of a family with hereditary non-polyposis colorectal cancer.

Mucosal proliferation was studied in biopsies obtained from the ascending colon from four mutation positive members of a hereditary non-polyposis colorectal cancer family (group I) and compared to subjects with some positive family history of colorectal cancer but lacking the clinical and pathological features of hereditary non-polyposis colorectal cancer (group II). Labelling indices were derived through immunohistochemical staining of the cell cycle associated nuclear proteins proliferating cell nuclear antigen (PCNA) and Ki-67. Only perfectly longitudinally sectioned crypts were assessed and good intra- and interobserver reproducibility was demonstrated. The labelling indices and proliferative compartment locations were similar in both groups. The mean Ki-67 derived labelling indices (group I 18.0% and group II 17.5%) were similar to values obtained for normal subjects in other studies. PCNA derived labelling indices (group I 58.5% and group II 57.0%) were high, but probably reflect optimization of staining through methacarn fixation. The negative findings do not fit with most published data but critical appraisal of the literature indicates that they are likely to be correct.

Adult↗
PubMed1997

Clinical and molecular features of the hereditary mixed polyposis syndrome.

BACKGROUND & AIMS: Various inherited syndromes predispose to the development of colonic juvenile polyps and colorectal cancer, with potential importance for sporadic tumorigenesis. This study describes features of a possibly new syndrome of atypical juvenile polyps and other colonic tumors and compares these features with those of known gastrointestinal tumor syndromes. METHODS: A large family, St. Mark's family 96, with a tendency to develop colonic polyps of mixed histological types is described. Genetic linkage to known polyposis syndromes has been tested. RESULTS: Adenomatous and hyperplastic polyps occur in affected members of the family, although the characteristic lesion is an atypical juvenile polyp. Some affected individuals have developed polyps of more than one type, and individual polyps may contain features of more than one histological type. Polyps can undergo malignant change. Typically, fewer than 15 polyps are found at colonoscopy and there is no extracolonic disease associated with the development of polyps. The family's polyps seem to be inherited in an autosomal-dominant fashion, but the disease is probably unlinked to candidate loci with importance in colorectal tumorigenesis, such as APC, hMSH2, and hMLH1. CONCLUSIONS: We term this family's disease hereditary mixed polyposis syndrome (HMPS). Although mutations in the putative HMPS gene may be responsible for syndromes such as juvenile and Peutz-Jeghers polyposes, HMPS may also be a distinct disease.

Adenomatous Polyposis Coli↗
PubMed1997

Mixed epithelial polyps in association with hereditary non-polyposis colorectal cancer providing an alternative pathway of cancer histogenesis.

A member of a hereditary non-polyposis colorectal cancer (HNPCC) family developed two colorectal cancers and multiple polyps within four years of a negative colonoscopic examination. One of the cancers was only 4 mm in diameter and showed the gross and endoscopic appearances of a de novo carcinoma. Microscopic examination of multiple levels revealed a mixed hyperplastic polyp/adenoma (mixed polyp) in contiguity with the cancer. The colon harboured additional polyps of which five were tubular adenomas, seven were hyperplastic polyps and seven were mixed polyps (architecturally compatible with hyperplastic polyps but with atypical cytology). Atypical features of the mixed polyps included tripolar mitoses, bizarre chromatin aggregations and multinucleation. One mixed polyp showed DNA microsatellite instability. Under the influence of the mutator defect, hyperplastic polyps may develop atypical or adenomatous features and show progression to carcinoma. Such an alternative morphogenetic pathway could explain the differing molecular and pathological profiles of cancers showing DNA microsatellite instability.

Adenomatous Polyps↗
PubMed1997

Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy. International Collaborative Group on HNPCC.

OBJECTIVE: The authors analyzed the incidence of rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC) after an abdominal colectomy. SUMMARY BACKGROUND DATA: The treatment of choice for a newly diagnosed patient with HNPCC with colon cancer is an abdominal colectomy. The incidence of rectal cancer after abdominal colectomy in HNPCC is not known. MATERIALS AND METHODS: A questionnaire was mailed to all International Collaborative Group on HNPCC members to identify patients in whom rectal cancer developed after total, subtotal or completion colectomy. Statistics were performed using the log-rank test, Kaplan-Meier method, and Cox's proportional hazards model. RESULTS: Rectal cancer developed in 8 (11%) of 71 patients a median of 158 months (range, 38-282 months) from their primary procedure. Of these eight patients, adenomas in the rectal mucosa developed in five at risk either before (4) or synchronous (1) with the diagnosis of rectal cancer. At the time of diagnosis of rectal cancer, six of eight patients were being observed. Age at first procedure and whether the patient was under surveillance were the only significant variables (p < 0.05) in the multivariate analysis in terms of rectal cancer risk. The risk of developing rectal cancer was estimated to be 3% every 3 years after abdominal colectomy for the first 12 years. CONCLUSIONS: The risk of rectal cancer in patients with HNPCC after an abdominal colectomy is approximately 12% at 12 years. Age at first surgical procedure and surveillance correlated with rectal cancer risk. Aggressive endoscopic surveillance of the rectum should be performed after abdominal colectomy.

Abdomen↗
PubMed1997

MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas.

AIMS: To examine the expression of MUC1 and MUC2 apomucins and distribution of MUC phenotypes (MUC2+/ MUC-, MUC2+/MUC1+, MUC2-/ MUC1+, MUC2-/MUC1-) in colorectal tubular adenomas in order to compare the distribution of phenotypes in flat and polypoid adenomas. METHODS: Endoscopically resected specimens of 35 flat and 15 polypoid tubular adenomas measuring less than 10 mm were examined and compared for the expression of MUC1 (MUSE11) and MUC2 (CCP58) and combined MUC phenotype distribution using conventional immunohistochemistry. RESULTS: There was no significant difference between flat and polypoid adenomas in their expression of MUC1 and MUC2 and the MUC phenotype distribution when stratified by grade of histological atypia. Adenomas with low grade atypia showed more extensive MUC2 expression than MUC1 (MUC2+/MUC1-phenotype). Expression of MUC1 was more extensive in adenomas with high grade atypia and the majority displayed either MUC2+/ MUC1+ or MUC2-/MUC1+ phenotypes. CONCLUSIONS: MUC2/MUC1 phenotypes were similar in flat and polypoid adenomas when stratified by grade of atypia. High grade atypia was characterised by reduced MUC2 and increased MUC1 expression in both types of adenoma. The phenotype MUC2-/MUC1+ occurs in tubular adenomas and cannot be a specific marker for de novo colorectal cancer.

Adenoma↗