Molecular evidence of field cancerization in a patient with 7 tumors of the aerodigestive tract

doi:10.1016/S0046-8177(00)80234-8

Human Pathology

Volume 31, Issue 2, February 2000, Pages 269-271

https://doi.org/10.1016/S0046-8177(00)80234-8 Get rights and content

Exposure of the mucosa of the upper aerodigestive tract to carcinogens can induce genetic changes resulting in various independent clones of neoplastic growth, a concept defined as “field cancerization.” The risk of developing multiple tumors in this compartment of the body is well established. We studied 6 distinct tumors of the upper aerodigestive tract of a single patient for loss of heterozygosity (LOH), microsatellite instability (MSI), p53 mutations, and K-ras codon 12 point mutations. We detected a unique pattern of LOH and p53 mutations in all 6 tumors. No tumor showed a K-ras mutation or MSI. The results support the mechanism of “field cancerization” and illustrate the potential power of molecular techniques to elucidate pathogenesis.

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Cited by (20)

Prevalence of synchronous second primary malignancy: Identification using whole body PET/CT imaging
2014, Clinical Imaging
Citation Excerpt :
Synchronous malignancy in the head and neck, lung, aerodigestive tract, ovary and prostate is explained by the concept of ‘field cancerization’. It is postulated that their epithelial cells are exposed to common carcinogens which lead to a vast and diverse area of genetically altered cancer fields and hence double primaries could synchronously or metachronously occur [12]. However, whether this concept can be applied to other tumors such as lymphoma is still unclear.
To describe the prevalence of synchronous second primary malignancy detected by PET/ CT in our clinical practice and its differentiating features from metastatic lesion.
All PET/CT scans from 1st October 2009 to 30th September 2010 were reviewed. The suspected cases of synchronous second primary malignancy detected by PET/CT were selected, and the histologically confirmed ones were being illustrated. Metachronous second primary cases were excluded.
A total of 1522 scans were reviewed. sixty-eight cases were suspected to have a synchronous second primary while 8 were histologically confirmed. Seven (0.4%) of them were malignant and 1 was a benign tumor. These 7 cases were illustrated, and we found a significant difference in SUVmax values and site of occurrence unusual to metastasis that were the two main radiological features differentiating them from metastatic lesion.
Synchronous second primary malignancy could be missed without the use of whole body imaging. Its diagnosis is of utmost importance to prevent erroneous upstaging of disease and subsequent palliative treatment instead of curative surgery.
Impact of <sup>18</sup>F-FDG PET/CT on the therapeutic management in the initial staging of the esophageal cancer
2009, Revista Espanola de Medicina Nuclear
La incidencia del carcinoma de esófago se ha incrementado considerablemente en los últimos años, siendo en la actualidad la sexta causa más frecuente de muerte por cáncer. El objetivo de nuestro estudio es comparar la utilidad de la PET/TAC con ¹⁸F-FDG y la TAC en la estadificación inicial en pacientes con carcinoma esofágico.
Se han valorado de manera retrospectiva 59 pacientes (6 mujeres) diagnosticados de una neoplasia esofágica. A todos los pacientes se les realizó una TAC y una PET/TAC de estadificación inicial entre 3 y 15 días después del diagnóstico.
La PET/TAC mostró el atrapamiento intracelular de ¹⁸F-FDG de significación patológica en todos los tumores (100%), signos de infiltración ganglionar locorregional (N1) en 34 y un total de 19 lesiones compatibles con metástasis (M1) en 14 pacientes (23,72%). La TAC mostró la lesión tumoral en 57 pacientes (96,6%), infiltración ganglionar en 32 pacientes y 17 M1 en 12 pacientes (20,33%). En tres casos la PET/TAC detectó la lesión esofágica de manera sincrónica en estudios de estadificación de otros procesos neoplásicos (pulmón y área otorrinolaringológica).
La PET/TAC mostró una mayor detección de lesiones tumorales primarias, así como adenopatías infiltradas y metástasis a distancia. Sólo se observó un cambio de estadificación en dos pacientes.
The incidence of esophageal cancer has increased considerably over recent years, it now being the 6^th most frequent cause of cancer-related death. Our study has aimed to compare the clinical value of PET/CT and CT scan in the initial staging of patients with esophageal cancer.
Fifty nine patients (6 women) diagnosed of esophageal cancer were assessed retrospectively. All patients underwent diagnostic CT scan and PET/CT for initial staging within 3 to 15 days following clinical diagnosis.
PET/CT showed intracellular ¹⁸F-FDG entrapment having pathological significance in all the tumors (100%), signs of locoregional lymph node infiltration (N1) in 34 and a total of 19 lesions consistent with metastasis (M1) in 14 patients (23.72%). The CT scan detected malignancy in 57 patients (96.6%), abnormal lymph node in 32 patients and 17 N1 in 12 patients (20.33%). In three cases, CT- PET detected synchronous esophageal lesion in staging studies for other neoplastic processes (lung and ear-nose-throat).
PET/CT showed a higher detection rate of primary malignant lesions, abnormal lymph nodes and distant metastases. A change in stage was only observed in two patients.
Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck
2002, Cancer Genetics and Cytogenetics
Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex karyotypic changes, and a substantial proportion of the reported tumors have shown intratumor heterogeneity in the form of cytogenetically related (40%) or unrelated clones (20%). In order to study intratumor heterogeneity and to distinguish the temporal order of chromosome rearrangements in these tumors, two or more samples from different areas of the same tumor were separately examined in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample heterogeneity was observed in 16 samples. Two samples displayed both related and unrelated multiple clones, four samples showed only multiple unrelated clones, and the remaining 10 samples had only related subclones. Intersample heterogeneity was detected in all but one tumor. Five tumors showed both cytogenetically related and unrelated multiple clones, 11 were found to have only related subclones, and the remaining two tumors showed only unrelated clones. Clonal evolution could be assessed in 13 tumors. A comparison of chromosome imbalances in different subclones from these tumors suggests that partial or entire loss of 3p, 8p, 9p, and 18q and gain of genetic material from 3q and 8q are likely to be early genetic events. In contrast, loss of 1q, 6p, 7q, and chromosome 10, as well as gain of chromosome arms 5p and 7p, are most probably later genetic events. One of the examined tumors contained two highly complex clones that were cytogenetically unrelated, indicating that this tumor had a multicellular origin.
Molecular evidence for the same clonal origin of both components of an adenosquamous Barrett carcinoma
2002, Gastroenterology
Citation Excerpt :
For practical purposes it is important to realize that patients with Barrett esophagus carry a risk not only for Barrett carcinoma but also for carcinomas at other sites of the upper aerodigestive tract.6
We describe an uncommon case of adenosquamous carcinoma arising in a Barrett esophagus in a 72-year-old white man who occasionally used alcohol, and was a nonsmoker for 34 years. Polymerase chain reaction–based microsatellite analysis was performed on the adenocarcinoma component (AC) and squamous cell carcinoma component (SC) of the tumor. The metaplastic Barrett epithelium (BE), the AC and the SC all showed loss of the same allele at 4 markers on chromosome 9p. Furthermore, the AC and the SC both showed loss of the same allele at all informative markers tested on chromosomal arms 3p, 5q, 10q, 14q, and 18q. In addition, both the SC and AC component contained the same missense mutation in the p53 tumor-suppressor gene. The only observed difference was a shift at a marker on chromosome 16q in the AC, whereas no shift was found in the BE and the SC. These findings suggest that this biphasic tumor has a monoclonal origin. The divergence presumably occurred late in the tumorigenesis of this carcinoma.
GASTROENTEROLOGY 2002;122:784-788
An in silico study on the detectability of field cancerization through parenchymal analysis of digital mammograms
2023, Medical Physics
A case of metachronous triple carcinoma with synchronous double primary carcinoma on<sup>18</sup>F-fluorodeoxyglucose positron emission tomography-computed tomography
2020, Indian Journal of Nuclear Medicine

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Human Pathology

References (12)

Multiple primary cancer in patients with cancer of the head and neck: Second cancer of the head and neck, esophagus and lung

Int J Radiat Oncol Biol Phys

A patient with seven primary tumors of the upper aerodigestive tract: The process of field cancerization versus distant monoclonal expansion [see comments]

Dis Esophagus

“Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin

Cancer

Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract

Cancer Res

Distinguishing second primary tumors from metastases in patients with head and neck squamous cell carcinoma

J Natl Cancer Inst

Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung

Cancer Res

Cited by (20)

Prevalence of synchronous second primary malignancy: Identification using whole body PET/CT imaging

Impact of <sup>18</sup>F-FDG PET/CT on the therapeutic management in the initial staging of the esophageal cancer

Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck

Molecular evidence for the same clonal origin of both components of an adenosquamous Barrett carcinoma

An in silico study on the detectability of field cancerization through parenchymal analysis of digital mammograms

A case of metachronous triple carcinoma with synchronous double primary carcinoma on<sup>18</sup>F-fluorodeoxyglucose positron emission tomography-computed tomography

Case StudyMolecular evidence of field cancerization in a patient with 7 tumors of the aerodigestive tract

Int J Radiat Oncol Biol Phys

A patient with seven primary tumors of the upper aerodigestive tract: The process of field cancerization versus distant monoclonal expansion [see comments]

Dis Esophagus

“Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin

Cancer

Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract

Cancer Res

Distinguishing second primary tumors from metastases in patients with head and neck squamous cell carcinoma

J Natl Cancer Inst

Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung

Cancer Res

Case Study
Molecular evidence of field cancerization in a patient with 7 tumors of the aerodigestive tract