Original contributionAbnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival
Section snippets
Tissue samples
Paraffin-embedded, formalin-fixed tissue blocks of resected gastric adenocarcinomas from 67 patients (mean age, 66 years; range, 32 to 88 years; 48 male and 19 female) were retrieved from the histopathology archives of the Royal London and St. Bartholomew’s Hospitals. No patient had received preoperative chemotherapy. Slides of primary tumors (n = 67) and lymph node metastases (n = 40) stained with hematoxylin and eosin were examined by a histopathologist (R.M.F.). Each tumor was graded as
Carcinomas
Of the 67 carcinomas, 5 were well differentiated, 30 were moderately differentiated, and 32 were poorly differentiated. Eighteen were of the signet ring cell type. Nine were categorized as UICC stage 1, 8 as stage 2, 28 as stage 3, and 22 as stage 4.
Cyclin D1
Cyclin D1 overexpression (≥5% expression) was seen in 37 (55%) of the carcinomas; >10% expression was seen in 21% of the carcinomas (mean, 6.4%; range, 0.6% to 20%) (Fig 1A).
pRb
Nonneoplastic gastric mucosa showed variable pRb expression. Staining was
Discussion
Inactivating mutations and deletions of Rb and p16 and associated loss of expression are found in many different cancers. Cyclin D1 amplification with overexpression is also common.12, 15, 17, 18, 28 Existing data suggest that abnormalities of pRb, p16, and cyclin D1 play a role in the pathogenesis of gastric cancer.22, 23, 24, 25 Comparisons are hampered by variable criteria for pRb and p16 loss,12, 13, 15, 17, 28 but (comparing directly whenever possible) <10% p16 expression, <50% pRb
Acknowledgements
The authors thank Professor Elisabeth Brambilla, Centre Hospitalier Universitaire de Grenoble, France, for kindly supplying the external positive controls as a gift. They also thank Alex Brown, Department of Histopathology, for technical support.
References (34)
- et al.
Differences in diagnostic criteria for gastric carcinoma between Japanese and Western pathologists
Lancet
(1997) Cyclin-dependent kinase inhibitors—A novel class of prognostic indicators
Hum Pathol
(2001)- et al.
Loss of RB and MTS1/CDKN2 (p16) expression in human sarcomas
Hum Pathol
(1997) - et al.
Loss of p16/CDKN2A tumor-suppressor protein in gastric adenocarcinoma is associated with Epstein-Barr virus and anatomic location in the body of the stomach
Hum Pathol
(2000) - et al.
p53, p16 and RB expression in adenosquamous and squamous cell carcinomas of the stomach
Pathol Res Pract
(1999) - et al.
Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer
Br J Cancer
(1995) - et al.
Evaluation of the new American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification
Cancer
(1999) - et al.
TNM Classification of Malignant Tumours
(2002) - et al.
Pathology and prognosis of gastric carcinomaWell versus poorly differentiated type
Cancer
(2000) - et al.
Prognostic comparison of the pathological classifications of gastric cancer. A population-based study
Histopathology
(1998)
Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma, with respect to histological subtypes and stages
J Gastroenterol Hepatol
bcl-2 expression as a prognostic factor of survival of gastric carcinoma
Anticancer Res
Expression of cell-cycle regulatory proteins cyclin D1, cyclin E, and their inhibitor p21 WAF/CIP in gastric cancer
J Pathol
Prognostic value of vascular endothelial growth factor expression in gastric carcinoma
Cancer
Expression of p16 and lack of pRB in primary small cell lung cancer
J Pathol
Prognosis for G1 cell-cycle regulatorsUseful for predicting course of disease and for assessment of therapy in cancer
J Pathol
Alterations of expression of Rb, p16(INK 4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance
J Pathol
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