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Factor Alteration Tumour suppressor genes p53 60% mutation -- high-grade intraepithelial neoplasia and carcinoma APC Late in intraepithelial neoplasia-carcinoma sequence FHIT Common, early abnormalities CDKN2A (p16 INK4A ) Hypermethylation common in intraepithelial neoplasia Growth factor receptors CD95/APO/Fas Shift to cytoplasm in carcinoma EGFR Expressed in 60% of carcinomas, gene amplification c-erbB2 Late in dysplasia-carcinoma sequence, gene amplification Cell adhesion E-cadherin Loss of expression in intraepithelial and invasive carcinoma Catenins Similar loss of expression to E-cadherin Proteases UPA Prognostic factor in carcinoma Proliferation Ki-67 Abnormal distribution in high-grade intraepithelial neoplasia Membrane trafficking rab11 High expression in low-grade intraepithelial neoplasia Table 5.9 Genes and proteins involved in the development of adenocarcinoma from Barrett oesophagus. Fig. 5.79 A highly infiltrative adenocarcinoma in a Barrett oesophagus. 226 Human cancers by organ site Mutation of the p53 gene is common in the early stages of adenocarcinoma of the oesophagus (Table 5.9). The presence of a p53 mutation in Barrett mucosa and in dysplasia may precede the development of adenocarcinoma. In high-grade dysplasia, a prevalence of p53 mutations of approximately 60% is found, similar to that found in adenocarcinoma. Almost half of these are C to T transitions at dipyrimidine sites (CpG islands). Alteration in transcription of FHIT and of p16 INK4A may be early events in adenocarcinoma. In contrast, a number of other loci are altered at a relatively late stage with no obligate sequence of events. Prevalent changes (>50%) include loss of heterozygosity on chromosomes 4q, 5q (several loci including APC), 17p and amplification of the gene encoding cerbB2. Molecules involved in membrane traffic, such as rab11, have been reported to be specific for the loss of polarity (rounding-up of cell nuclei) seen in lowgrade dysplasia. In invasive oesophageal adenocarcinoma, reduced expression of the cadherin/catenin complex and increased expression of various proteases is detectable [15]. Management Endoscopic ultrasonography is used to evaluate both depth of tumour infiltration and para-oesophageal lymph node involvement. In advanced carcinomas, CT and MRI give information about local and systemic spread. Tumour growth is characterized as swelling of the oesophageal wall, with or without direct invasion to surrounding organs. The primary treatment for local disease is oesophagectomy. This surgical approach is rarely curative (eventually 85 to 90% of the patients die of recurrent disease) but palliation of dysphagia is an important secondary objective. Placement of a prosthetic tube or stent across the tumour stenosis (narrowing) may be indicated to restore swallowing in patients not suitable for surgery. Radiotherapy (external beam or brachytherapy) as well as multiple chemotherapeutic protocols have also been proposed (alone or combined with surgery), but these approaches are rarely curative. Palliation with radiation alone is an alternative to surgery, particularly if combined NSW, Australia USA (Whites) Netherlands Osaka, Japan Shanghai, China USA (Blacks) France Slovakia Madras, India Denmark Qidong, China Chiang Mai, Thailand 5 13.7 13.2 12 11.7 11.2 9.1 9 8 6.5 4.2 3.8 0 50 100 % survival, both sexes Fig. 5.80 Five-year relative survival after diagnosis of oesophageal cancer.
with a stent; laser recannulation, alcohol injection and dilation may be used to maintain the oesophageal lumen [8]. Prognostic factors include stage at diagnosis, patient’s general health, morpho- REFERENCES 1. Muñoz N, Day NE (1996) Esophageal cancer. In: Scottenfeld D, Fraumeni FJ eds, Cancer Epidemiology and Prevention, Oxford, New York, Oxford University Press, 681-706. 2. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J, eds (1997) Cancer Incidence in Five Continents, Vol. VII (IARC Scientific Publications No. 143 and IARC Cancerbase No. 2), Lyon, IARCPress. 3. Launoy G, Milan CH, Faivre J, Pienkowski P, Milan CI, Gignoux M (1997) Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption, mean intake and current and former consumption. Br J Cancer, 75: 1389-1396. 4. De Stefani E, Muñoz N, Esteve J, Vasallo A, Victora CG, Teuchmann S (1990) Mate drinking, alcohol, tobacco, diet, and esophageal cancer in Uruguay. Cancer Res, 50: 426- 431. 5. de Villiers EM, Lavergne D, Chang F, Syrjanen K, Tosi P, Cintorino M, Santopietro R, Syrjanen S (1999) An interlaboratory study to determine the presence of human papillomavirus DNA in esophageal carcinoma from China. Int J Cancer, 81: 225-228. 6. Spechler SJ, Goyal RK (1986) Barrett's esophagus. N Engl J Med, 315: 362-371. 7. Goodnight J, Venook A, Ames M, Taylor C, Gilden R, Figlin RA (1996) Practice Guidelines for Esophageal Cancer. Cancer J Sci Am, 2: S37. 8. Law S, Wong J (1998) Cancer of the Esophagus. In: Morris D, Kearsley J, Williams C eds, Cancer: A comprehensive clinical guide, Harwood Academic Publishers, 155- 162. 9. Gabbert HE, Shimoda T, Hainaut P, Nakamura Y, Field JK, Inoue H (2000) Squamous cell carcinoma of the logical and molecular features of the tumour, for squamous cell carcinoma the depth of invasion and for adenocarcinoma presence of lymphatic metastases. Overall five-year relative survival rates are oesophagus. In: Hamilton SR, Aaltonen LA, eds, World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System, Lyon, IARCPress, 11-19. 10. Taniere P, Martel-Planche G, Puttawibul P, Casson A, Montesano R, Chanvitan A, Hainaut P (2000) TP53 mutations and MDM2 gene amplification in squamous-cell carcinomas of the esophagus in south Thailand. Int J Cancer, 88: 223-227. 11. Mandard AM, Hainaut P, Hollstein M (2000) Genetic steps in the development of squamous cell carcinoma of the esophagus. Mutat Res, 462: 335-342. 12. Montesano R, Hollstein M, Hainaut P (1996) Genetic alterations in esophageal cancer and their relevance to etiology and pathogenesis: a review. Int J Cancer, 69: 225- 235. 13. Yokoyama A, Muramatsu T, Ohmori T, Yokoyama T, Okuyama K, Takahashi H, Hasegawa Y, Higuchi S, Maruyama K, Shirakura K, Ishii H (1998) Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis, 19: 1383-1387. 14. Werner M, Flejou JF, Hainaut P, Höfler H, Lambert R, Keller G, Stein HJ (2000) Adenocarcinoma of the oesophagus. In: Hamilton SR, Aaltonen LA eds, World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System, Lyon, IARCPress, 20-26. 15. Tselepis C, Perry I, Jankowski J (2000) Barrett's esophagus: disregulation of cell cycling and intercellular adhesion in the metaplasia-dysplasia-carcinoma sequence. Digestion, 61: 1-5. poor (Fig. 5.80), survival ranging from about 10% in patients with squamous cell carcinoma to 20% in patients with adenocarcinoma. WEBSITE NCI Esophageal Cancer Homepage: http://www.cancer.gov/cancer_information/cancer_type/ esophageal/ Oesophageal cancer 227
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WORLD HEALTH ORGANIZATION WHO OMS I
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WORLD CANCER REPORT Editors Bernard
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CONTENTS Foreword 9 1 The global bu
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The global burden of cancer Cancer
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Fig. 1.2 Incidence and mortality of
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Central and Southern Europe differ
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Incidence of cancer in South Centra
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from documentation of disease to a
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TOBACCO SUMMARY >In addition to lun
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Fig. 2.3 Smoking by children is inc
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Cancers positively Sex Standardized
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PHARMACOLOGICAL APPROACHES TO SMOKI
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level the dose—response relations
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lipoprotein-associated cholesterol,
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Agent Cancer site/cancer Main indus
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Industry, occupation Cancer site/ca
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to occupational exposures in develo
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Air pollutant WHO Air Quality Guide
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der cancer of the order of 50% is p
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AFLATOXIN B 1 HEPATITIS VIRUS (chro
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Fig. 2.30 Correlation between regio
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MEDICINAL DRUGS SUMMARY > Certain d
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Drug or drug combination Cancer IAR
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Agent or substance Cancer site/canc
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sources of electromagnetic fields [
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CHRONIC INFECTIONS SUMMARY > Infect
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Infection Subclinical Mutagenic fac
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TUMOURS ASSOCIATED WITH HIV/AIDS Ap
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DIET AND NUTRITION SUMMARY > Up to
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Fig. 2.54 The age-adjusted mortalit
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OVERWEIGHT, OBESITY AND PHYSICAL AC
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IMMUNOSUPPRESSION SUMMARY >Persiste
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Fig. 2.64 Cancer following immunosu
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Syndrome Gene Location Cancer site/
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viduals, confirmation of a gene def
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REPRODUCTIVE FACTORS AND HORMONES S
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PHYTO-ESTROGENS AND CANCER PEVENTIO
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Indicator Number of oral contracept
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Mechanisms of tumour development Th
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The stages in tumorigenesis have be
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PRECURSOR LESIONS IN CHEMOPREVENTIO
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CARCINOGEN ACTIVATION AND DNA REPAI
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adducts, a few weeks or months for
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I Reactive oxygen species Methylati
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which remove the mismatched bases,
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Common human oncogenes Many common
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product of the RB1 gene (pRb) and a
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ates a molecular bridge between p53
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potential cancer genes altered thro
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One of the earliest genes to be ide
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Regulation of the cell cycle and co
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CELL-CELL COMMUNICATION SUMMARY > C
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Connexin genes and tumour suppressi
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APOPTOSIS SUMMARY > The term apopto
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Caspase-8 Caspase-3 c-FLIP Procaspa
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ways. Several options are under inv
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INVASION AND METASTASIS SUMMARY > T
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laminin, entactin and also heparan
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Target Example of agent Comments Ad
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organs, and to respond to local gro
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TOBACCO CONTROL SUMMARY > Tobacco-i
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Region Deaths due to % of total dea
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ipated, is primarily attributable t
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smoke. This may be achieved in part
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there is no evidence for the effica
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industries, processes and occupatio
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stoves arises in rural areas of dev
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Climbing plants on trellis at end r
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HEPATITIS B VACCINATION SUMMARY > P
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Fig. 4.17 Chronic active HBV-associ
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HUMAN PAPILLOMAVIRUS VACCINATION SU
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Vaccine Site of trial Number of pat
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prolonged use. Similar drugs, that
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aspirin and other non-steroidal ant
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SCREENING FOR BREAST CANCER SUMMARY
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Fig. 4.35 Cumulative mortality from
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SCREENING FOR PROSTATE CANCER SUMMA
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Fig. 4.39 Poster designed for an an
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is around 10% for cancer (out of ev
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45 with one positive rehydrated FOB
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eing based on (i) time trends in th
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Fig. 4.48 Women at a clinic in Indi
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SCREENING FOR ORAL CANCER SUMMARY >
Page 169 and 170: India will provide useful informati
Page 171 and 172: cer incidence following cure of inf
Page 173 and 174: 100 50 25 10 5 2.5 1 Japan Males Fe
Page 175 and 176: Human cancers by organ site Maligna
Page 177 and 178: tobacco smoking: age at start, aver
Page 179 and 180: diagnosis is usually confirmed by h
Page 181 and 182: is frequent and survival rates are
Page 183 and 184: Fig. 5.14 Physician reading digital
Page 185 and 186: Markers of prognosis in breast canc
Page 187 and 188: cer in the contralateral breast (Ch
Page 189 and 190: 100 50 25 10 5 2.5 1 Japan Chile Po
Page 191 and 192: depends on staging. Small intramuco
Page 193 and 194: Fig. 5.30 A diet rich in fresh frui
Page 195 and 196: ane protein involved in cell adhesi
Page 197 and 198: LIVER CANCER SUMMARY > About 560,00
Page 199 and 200: Fig. 5.39 A woman in the Gambia pre
Page 201 and 202: REFERENCES 1. Ferlay J, Bray F, Par
Page 203 and 204: Certain Possible Uncertain Age Andr
Page 205 and 206: Management The dramatic division be
Page 207 and 208: TUMOUR NORMAL Gastrula PGC 2n Impri
Page 209 and 210: CANCERS OF THE FEMALE REPRODUCTIVE
Page 211 and 212: Fig. 5.62 Five-year relative surviv
Page 213 and 214: Inheritance of high-penetrance gene
Page 215 and 216: invasive malignant. Malignant germ
Page 217 and 218: OESOPHAGEAL CANCER SUMMARY >Cancer
Page 219: Fig. 5.76 A radiographic view of an
Page 223 and 224: Fig. 5.82 Risk of bladder cancer am
Page 225 and 226: Partial cystectomy is appropriate f
Page 227 and 228: poorly known since hypopharyngeal c
Page 229 and 230: Fig. 5.92 Oral leukoplakia with mil
Page 231 and 232: LYMPHOMA SUMMARY > Malignant lympho
Page 233 and 234: T Fig. 5.101 Nuclear magnetic reson
Page 235 and 236: Fig. 5.106 Five-year relative survi
Page 237 and 238: Fig. 5.109 The immediate aftermath
Page 239 and 240: A B Fig. 5.113 Acute myeloid leukae
Page 241 and 242: Fig. 5.118 Five-year relative survi
Page 243 and 244: Fig. 5.120 Age-specific incidence a
Page 245 and 246: Hereditary condition Mode of inheri
Page 247 and 248: MELANOMA SUMMARY > Approximately 13
Page 249 and 250: Fig. 5.131 Primary melanoma with a
Page 251 and 252: THYROID CANCER SUMMARY > Cancer of
Page 253 and 254: Papillary carcinoma RET/PTC TRK BRA
Page 255 and 256: KIDNEY CANCER SUMMARY > Cancer of t
Page 257 and 258: Stage Clear cell carcinoma Papillar
Page 259 and 260: TUMOURS OF THE NERVOUS SYSTEM SUMMA
Page 261 and 262: ing the optic tract, brain stem and
Page 263 and 264: mut = mutant p53 wt = wildtype p53
Page 265 and 266: SURGICAL ONCOLOGY SUMMARY > Surgica
Page 267 and 268: Year Radical mastectomy (%) Modifie
Page 269 and 270: TELEMEDICINE The prospects for tele
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Equipment Energy 50% depth dose App
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CANCER EDUCATION IN MEDICAL COURSES
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Fig. 6.10 Crystals of cisplatin: mo
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Responsiveness Cancer (in decreasin
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Most of the world’s most common c
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treatment of cancer. The problems l
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duction. It is clear that tumour ce
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REHABILITATION SUMMARY > Rehabilita
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cer and its associated disability.
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REFERENCES 1. Garden FH, Gillis TA
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Cancer pain relief varies and in so
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EMERGING ISSUES IN PALLIATIVE CARE
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Cancer control The negative impact
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priority to cancer control activiti
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Prevention of cancer Every country
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- Assessing the magnitude of the ca
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high-risk women. Further details on
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ecords departments are either rudim
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THE INTERNATIONAL AGENCY FOR RESEAR
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in the capitals/urban areas of four
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in the overall cancer strategy. WHO
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68% 1955 1975 1995 2025 32% 40% by
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Fig. 7.15 A grandfather at work in
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Fig. 7.17 Main causes of death in d
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Contributors and Reviewers Sources
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Dr Vera Luiz da Costa e Silva Tobac
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Georgia Moore Centers for Disease C
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REVIEWERS Dr Sandra E. Brooks 405 W
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2.53 T. Norat and E. Riboli, IARC 2
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Gastroenterology, 118(2 Suppl 1): S
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5.106 & 5.107 IARC/SEER/Osaka Cance
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4.17 R. Lambert, IARC/Adapted from
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Brain cancer, see nervous system tu
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Fibroblast growth factor (FGF), 117
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Microarray, 240 Micronutrients, 65,
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S Saccharin, 64, 85 Salicin, 153 Sa
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