Mucosa Of Upper Aerodigestive Tract Research Articles

The digestive Enzyme-Based nasal dysbiosis in Empty nose Syndrome: A theory

Empty nose syndrome (ENS) is described as an empty space in the region of the inferior and middle turbinates of patients who underwent inferior and middle turbinectomy. Patients commonly complained of dry nose, paradoxical nasal obstruction, and crust. Symptoms significantly worsen the quality of life of patients. The pathophysiology of ENS is poorly understood. Several abnormalities in the nasal airflow dynamics, air humidification and warming, mucociliary clearance, and trigeminal-related sensory function were reported but it is misunderstood why some patients with anatomical turbinate defects developed ENS, while others do not experience symptoms with similar anatomy. This paper proposes a theory associating the development of ENS with the presence of laryngopharyngeal reflux disease (LPRD). LPRD is associated with the deposit of gastroduodenal enzymes into the upper aerodigestive tract mucosa, which lead to a decrease of the defense mechanisms of mucosa (mucus hydration, bicarbonate secretion, growth factor production) and an increase of mucosa injuries. In ENS patients, the deposit of digestive enzymes into the nasal mucosa may lead to concurrent injuries of the nasal cells involved in air humidification, warming, or sensory function, and modifications of the nasal microbiome that cannot heal the injured mucosa.

Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Systematic classification of confocal laser endomicroscopy for the diagnosis of oral cavity carcinoma

IntroductionConfocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo microscope-like images of the upper aerodigestive tract's mucosa in 1000-fold magnification. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignoma suspected mucosa requires strict evaluation criteria. This study aims to validate a score for oral cavity squamous cell carcinoma (OCSCC) diagnostic. MethodsWe performed CLE and examined a total of twelve patients. All 95 sequences (778 s, 6224 images) originate from the area of the primary tumor 260 s, 2080 images) and unsuspicious mucosa of the oral cavity (518 s, 4144 images). Specimen were taken at corresponding locations and analyzed histologically in H&E staining as a reference standard. A total of eight examiners (four experienced and four inexperienced) evaluated the sequences based on a scoring system. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are inter-rater reliability and receiver operator characteristics. ResultsHealthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 88.7 %, 90.1 %, 87.4 %, 87.5 %, and 90.0 %, respectively, with inter-rater reliability and κ-value of 0.775, and an area under the curve of 0.935. ConclusionsThe results confirm that this scoring system is applicable in the oral cavity mucosa to classify benign and malignant tissue.

GMP compliant isolation of mucosal epithelial cells and fibroblasts from biopsy samples for clinical tissue engineering

Engineered epithelial cell sheets for clinical replacement of non-functional upper aerodigestive tract mucosa are regulated as medicinal products and should be manufactured to the standards of good manufacturing practice (GMP). The current gold standard for growth of epithelial cells for research utilises growth arrested murine 3T3 J2 feeder layers, which are not available for use as a GMP compliant raw material. Using porcine mucosal tissue, we demonstrate a new method for obtaining and growing non-keratinised squamous epithelial cells and fibroblast cells from a single biopsy, replacing the 3T3 J2 with a growth arrested primary fibroblast feeder layer and using pooled Human Platelet lysate (HPL) as the media serum supplement to replace foetal bovine serum (FBS). The initial isolation of the cells was semi-automated using an Octodissociator and the resultant cell suspension cryopreservation for future use. When compared to the gold standard of 3T3 J2 and FBS containing medium there was no reduction in growth, viability, stem cell population or ability to differentiate to mature epithelial cells. Furthermore, this method was replicated with Human buccal tissue, providing cells of sufficient quality and number to create a tissue engineered sheet.

Metastasis of prostate carcinoma to the thyroid cartilage presenting with airway obstruction

It is generally presumed that large neck masses resulting in airway obstruction are associated with a primary neoplastic problem in the upper aero-digestive tract mucosa, usually a carcinoma. Metastasis into...

Synchronous tumors in head neck oncology: A rare case and its management

Although double cancers in the upper aerodigestive tract mucosa are not uncommon collision tumors that are composed of a papillary thyroid carcinoma and a laryngeal giant cell tumour are rare. The term ‘synchronous tumor’ refers to the coexistence of two histologically distinct malignant tumors within the same mass. There are case reports of the Synchronous Tumour composed of papillary thyroid carcinoma with laryngeal squamous cell carcinoma. However, even isolated presentation of giant cell tumour of the larynx is very rare and only 8 cases have been reported. Giant cell tumors of the larynx (GCTL) are extremely rare benign tumors arising in the osteocartilaginous tissue of the larynx. Complete surgical resection is adequate for local control in all the reported cases. Radiation therapy and/or chemotherapy are not a necessary adjunct in the treatment of these laryngeal tumors. This paper reports the case of a 55-year-old male who presented with a synchronous tumor in the neck.

PO-275 Effect of ionising radiation in FaDu cell line- preliminary results

IntroductionHead and neck cancer includes malignancies usually originated in upper aerodigestive tract mucosa. Despite hypopharyngeal cancer has a low incidence, patients have poor prognosis, advanced stage and distant metastization. A low overall survival of these cancer might be explained by the presence of cancer stem cells (CSC). Identification of a CSCs markers panel could help to overcome this barrier allowing to develop target drugs. This study aims to evaluate and characterise the expression of proliferation, adhesion and CSC markers in a hypopharyngeal cell line (FaDu) before and after ionising radiation exposure.Material and methodsParaffin cell blocks were performed in order to evaluate by immunohistochemistry (IHC), epithelial characterisation (cytokeratin CAM 5.2, leukocyte common antigen (LCA), vimentin), tumoral aggressiveness (P16, P53, OCT4 and SALL4), proliferation (Ki-67) and CSC markers (EpCAM, CD10, CD44, CD117, CD133, beta-catenin). Also, 14 subtypes of high-risk HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 16, and 18), EBV, Akt and Wnt expressions were analysed. Radiotherapy was performed with 0.5 × 106 cells/mL, exposed to increasing doses of X-ray (0.5 to 10 Gy), except for control cells. Clonogenic assay and IHC were realised. Treated cells for IHC were fixed with alcohol 96%, 48 hour after treatment and posteriorly analysed the following antigens Ki-67, EpCAM, CD133, CD44, beta-catenin, CD117, CD10, Akt, Wnt, OCT4 and P53.Results and discussionsFaDu cell line showed positive immunostaining for cytokeratin, vimentin and negative to LCA. Relatively to tumoral aggressiveness, cells only expressed positively P16, while P53, OCT4 and SALL4 were negative. About proliferation it was observed Ki-67+. Between analysed stemness markers just CD44, CD133 and beta-catenin were expressed. Among HPV subtypes analysed only HPV18 was stained positive and EBV-. Adding, control cells expressed Akt +and Wnt +in normal conditions. Preliminary results related to ionising radiation effects showed that cell survival is X-ray dose dependent. Moreover, it was observed Wnt expression alterations with X-ray exposure.ConclusionThese results demonstrate that FaDu survival is affected by ionising radiation exposure. This may be associated with Wnt expression which is altered after irradiation, highlighting that this molecule is involved in cell fate determination, cell polarity, migration and cell proliferation.

Assessing field change through the expression of cytokeratin 18 and 19 in areas of erosive oral lichen planus and adjoining normal mucosa

Introduction: Oral lichen planus (OLP) is a potentially malignant disorder. Of its seven different clinical forms, erosive is most prone for malignant transformation. The concept of field cancerization postulates that the mucosa of upper aero-digestive tract has a potential for developing malignancy due to genetic abnormalities and migration of transformed cells. Cytokeratins (CKs) are intermediate filament proteins that are specifically expressed in epithelial tissues and used as tools in diagnostic pathology, particularly in the detection of tumors. Aim: To identify field change through the expression of CK 18 and 19 in areas of erosive OLP and adjoining normal mucosa (ANM) and assess whether CK 18 and 19 could predict malignant transformation. Materials and Methods: Tissue samples from 19 patients with erosive OLP were subjected to immunohistochemical analysis for CK 18 and 19. Results: CK 18 was expressed in 11 out of the 19 samples of erosive OLP, of which nine samples showed expression in ANM as well. CK 19 was expressed in 10 out of the 19 samples of erosive OLP, of which eight samples showed expression in ANM as well. Conclusion: Expression of CK 18 and 19 could be used to predict malignant transformation of erosive OLP and also aids in assessing field change.

Second primary tumor in patients with upper aerodigestive tract cancer

SummaryIn the first three years after treatment of patients with squamous cell carcinoma of upper aerodigestive tract (UADT), there is a high incidence of recurrences. After the third year, the occurrence of second primary tumor (SPT) is an important cause of morbimortality.AimTo evaluate the incidence and the characteristics of the SPT in patients with squamous cell carcinoma of UADT, treated with curative intention.MethodsRetrospective study where the incidence, localization and treatment of SPT had been analyzed and survival rates were calculated.ResultsOf the 624 analyzed cases, 59 (9.4%) had SPT during follow-up (4 synchronous and 55 metachronous). The SPT free survival rate ranged from 2 to 191.3 months (median of 42.5 months). In 20 cases (33.9%) the SPT was diagnosed after the fifth year of follow-up. The most frequent site of STP was the UADT mucosa (49.1%), followed by the lungs (22.0%) and the esophagus (11.9%). The best survival after-SPT occurred in cases of UADT STP (32.2% in 5 years, median 16.2 months).ConclusionThe STP incidence was 9.4%. In 33.9% of the cases, the SPT was diagnosed after the fifth year of follow-up. The most frequent localization of STP was the UADT mucosa.

Overview of Advances in Head and Neck Cancer.

The term head and neck cancer may refer exclusively to cancers arising from the upper aerodigestive tract or more broadly to any malignancy originating in the head and neck region. In this Special Series issue of Journal of Clinical Oncology, there is a major focus on squamous cell carcinomas arising from the upper aerodigestive tract mucosa. In addition, we also address nasopharyngeal cancer, nonmelanoma cutaneous head and neck cancer, and squamous carcinoma of the neck of unknown primary origin. The 16 articles in this issue provide the reader with an overview of current evidence and management, recent developments, and insights into future directions. The relatively recent recognition that human papillomavirus (HPV) is a cause of oropharyngeal cancer (OPC)— and that this is a distinct entity with different clinical and molecular features— has had a profound impact on the field. In this series, we include three articles that review our rapidly evolving understanding of HPV-related head and neck cancers. Hayes et al 1 review the molecular landscape of HPV-positive and -negative head and neck cancers after the recently published Cancer Genome Atlas analysis, 2 demonstrating significant molecular differences that may have therapeutic implications in the future. Gillison et al 3 review the epidemiology of HPV head and neck cancer and oral HPV infection, including the geographic variation in incidence and in the HPV-attributable fraction and the prospects for virus-specific cancer prevention. The overall better prognosis of HPV-associated OPC and the identification of a low-risk population with an excellent prognosis have led to concerns that our current treatments, mainly derived from trials of HPV-negative head and neck cancer, may be more intensive than is necessary. Bhatia and Burtness 4 review what is known about risk groups and describe de-escalation trials designed to maintain high cure rates with less toxicity.

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson's Disease Patients.

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Acantholytic Squamous Cell Carcinoma in Upper Aerodigestive Tract: Histopathology, Immunohistochemical Profile and Epithelial Mesenchymal Transition Phenotype Change

Acantholytic squamous cell carcinoma is a rare variant of squamous cell carcinoma in the mucosa of upper aerodigestive tract. Histomorphologically, acantholytic squamous cell carcinoma may lose the typical features of conventional squamous cell carcinoma and mimic other epithelial or mesenchymal malignancies due to advanced acantholysis and dyskeratosis. Because of its rarity, information of prognosis, pathologic features and immunohistochemical profiles is limited. We have studied clinicopathologic features and immunohistochemical profiles of four acantholytic squamous cell carcinoma cases arising from upper aerodigestive tract. Clinical results indicate an aggressive biologic behavior. Morphologically, all tumors revealed significant acantholysis with separation of tumor cells and intratumoral spaces. The tumor cells were highly pleomorphic and growth patterns were variable. In immunohistochemical studies, all tumor cells revealed positive reactions for AE1/AE3 and p63 supporting a squamous epithelial origin. In contrast to conventional aerodigestive squamous cell carcinoma, acantholytic squamous cell carcinoma showed significant reductions of cytokeratin19, E-cadherin and concomitant up-regulation of vimentin expression. Both morphologic features and immunohistochemical profiles indicate that acantholytic squamous cell carcinoma has acquired an epithelial mesenchymal transition phenotype. However, in contrast to other solid malignant tumors, the epithelial mesenchymal transition phenotype change in acantholytic squamous cell carcinoma is not limited to the invasive front of the peripheral tumor but, rather, diffusely involves entire neoplastic lesion. In addition, because cytokeratin 19 staining is attenuated, this would be an insensitive marker for following up and/or in detecting disseminated tumor cells in cases of acantholytic squamous cell carcinoma in upper aerodigestive tract.

The impact of EGFR stimulation and inhibition on BPDE induced DNA fragmentation in oral/oropharyngeal mucosa in vitro

Still, the vast majority of head and neck squamous cell carcinoma (HNSCC) can be linked to the "traditional" risk factors tobacco smoke and alcohol consumption. These tumors are believed to be the results of multiple years of carcinogenic impact on upper aerodigestive tract mucosa. The frequent observation, that one patient suffers from several synchronous cancers, multiple local recurrences, and second primary tumors led to the concept of field cancerization, first introduced by Slaughter and colleagues in 1953. As underlying molecular events, genetic instability, loss of heterozygosity, amplification, deletion, up- and down-regulation of oncogenes and/or tumor suppressor genes were revealed. One of the best studied oncogenic features of head and neck carcinogenesis are high expression levels of epidermal growth factor receptor (EGFR). Enhanced expression of the receptor was detected in histologically normal mucosa from HNSCC patients and increasing levels during the progress from hyperplasia to dysplastic lesion and invasive carcinoma were demonstrated. Whereas nearly all of our knowledge about EGFR biology in HNSCC is based on preclinical and clinical studies investigating receptor inhibitors, little is known about cause and function of EGFR in premalignant mucosa. In this study we show, that EGFR stimulation significantly decreases carcinogen induced DNA damage in normal mucosa from HNSCC patients and that this effect is completely abrogated adding an anti-EGFR antibody before stimulation, while there was no effect in non-tumor controls. The effect of EGFR inhibition was contrary. In non-tumor controls, blocking the receptor with an antibody significantly decreased DNA damage, whereas in cases no effect was seen. Our results indicate an important role of the receptor during chemical carcinogenesis. On the basis of this study we suppose, that increasing EGFR levels during head and neck carcinogenesis can be interpreted as a physiological response to permanent carcinogen impact on the mucosa.

Reduced risk of head and neck second primary tumors after radiotherapy

Background and purpose With radiotherapy of primary tumors of the head and neck, a significant dose reaches the surrounding mucosa. The field cancerization and second field tumor theories state that premalignant lesions are present in the mucosa even at the time of primary tumor treatment. We tested the hypothesis that exposure to irradiation stabilizes subclinical premalignant lesions. This would reduce the rate of second primary tumors in the upper aerodigestive tract (UADT). Materials and methods The cohort consisted of 346 patients treated for small localized squamous cell carcinoma of the oral cavity (T1–2, N0, and M0). The rate of UADT second primary tumors was compared between 247 patients exposed to radiation (case subjects) and 99 patients unexposed to radiation (control subjects). Results Median time to UADT second primary tumor was 8.6 years for irradiated patients and 3.9 years for controls ( p = 0.007). Through the first 5 years after the treatment of the primary tumor, the relative risk of developing a new UADT tumor for irradiated patients compared to controls was 0.12 ( p < 0.001). After 5 years the risk increased for irradiated cases. A corresponding change in risk was not found for controls. Conclusions A slower rate of second primary tumors was seen within UADT mucosa exposed to irradiation. This could suggest a preventive effect by radiation on malignant transformation of subclinical premalignant foci.

Balloon cell nevus of the pharynx

Mucosal melanotic lesions are rare, and the still rarer balloon cell variant has not been reported in the upper aerodigestive tract mucosa. We report a case of balloon cell nevus of the pharynx. A 35-year-old woman was seen with complaints of a black color in her mouth. Physical examination revealed a diffusely pigmented posterior pharyngeal wall. The pigmentation extended superiorly to the posterior edge of the palate, and laterally, it stopped short of the posterior tonsillar pillars. The overlying mucosa was smooth, with no swelling. Flexible endoscopy showed that the lesion extended to the cricopharynx. Findings on histopathologic examination were consistent with balloon cell nevus of the pharynx. Complete excision was not possible, because the lesion was very diffuse. After 2 years of conservative management and regular follow-up examinations, no change in the symptoms and no increase in the lesion have been seen. Melanotic lesions in the upper aerodigestive tract mucosa are rare. This case is reported for its rarity, unusual presentation, and characteristic histopathologic features.

MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract

Objectives: This study investigates MUC4 expression in normal squamous epithelia and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in salivary gland neoplasms. Study design: MUC4 antigens in tumor and adjacent normal tissue are localized by immunocytochemical studies. Fresh frozen tissues from surgical resection specimens are further analyzed by Western blot. Results: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph nodes. A trend toward decreased MUC4 staining in moderately and poorly differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed. Immunocytochemical staining of MUC4 in 13 major and minor salivary gland neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is demonstrated in immunoblots of normal parotid tissue and in the single parotid malignancy analyzed, but is not demonstrated in one minor salivary gland malignancy. These findings characterize normal UADT mucosal and salivary MUC4 expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors. Significance: Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors. (Otolaryngol Head Neck Surg 2001;124:127-41.)

Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin.

Unknown primary head and neck squamous cell carcinoma (HNSCC) presents as a cervical lymph node metastasis without identification of the primary tumor, despite thorough diagnostic work-up that includes physical examination, computed tomography, esophagoscopy, laryngoscopy, bronchoscopy, and multiple surveillance biopsies. We investigated whether the site of origin of the primary tumor could be localized in the upper aerodigestive tract mucosa by detection of genetic alterations identical to those found in metastatic lesions. Microsatellite analysis was performed on metastatic tumors obtained from 18 patients with unknown primary HNSCC. Histologically benign surveillance biopsy specimens were also analyzed. Patients were followed up to 13 years with continuing surveillance for primary mucosal tumors. Most patients were treated with neck dissection followed by radiation therapy to the affected neck and ipsilateral Waldeyer's ring. In 10 (55%) of the 18 patients, at least one histopathologically benign mucosal biopsy specimen from defined anatomic sites (i.e., most likely sites for an occult primary tumor) demonstrated a pattern of genetic alterations identical to that present in cervical lymph node metastases. One patient harboring genetic alterations in the base of the tongue and two patients harboring genetic alterations in a tonsillar fossa subsequently developed HNSCC in the identical or adjacent mucosal region; all three of the primary head and neck mucosal tumors that eventually appeared between 1 and 13 years later in these patients had genetic changes identical to those in the benign mucosal biopsy specimens and in the metastatic lymph nodes. These data support the hypothesis that histopathologically benign mucosa of the upper aerodigestive tract may harbor foci of clonal, preneoplastic cells that are genetically related to metastatic HNSCC and that such mucosal sites are the sites of origin of unknown primary HNSCC. Microsatellite analysis may represent a clinically useful tool for determining such sites.

Fluorescence spectroscopy: a technique with potential to improve the early detection of aerodigestive tract neoplasia.

Any innovation which facilitates the early detection of neoplastic changes in upper aerodigestive tract mucosa has potential to greatly improve survival and quality of life in persons prone to develop malignancies in this area. One technology that has shown great promise during initial investigations is fluorescence spectroscopy. Fluorescence spectroscopy evaluates the physical and chemical properties of tissue by analyzing the intensity and character of light emitted in the form of fluorescence. This technology has been investigated for the non-invasive detection of malignancy in various sites including the gastrointestinal tract, lung, breast, and cervix. This article reviews the recent work investigating the capabilities of fluorescence spectroscopy to discriminate between normal and neoplastic mucosa in the oral cavity. Also discussed are potential applications for the detection and diagnosis of premalignant and malignant lesions of the upper aerodigestive tract, and some of the obstacles to overcome to make this technology feasible.

Clonal chromosome aberrations accumulate with age in upper aerodigestive tract mucosa

Short-term cultured non-neoplastic upper aerodigestive tract (UAT) mucosa samples from 36 patients with squamous cell carcinoma of the head and neck (SCC) and 53 patients with benign UAT disorders were cytogenetically analyzed. The cell cultures were divided into two series: in series A, cells were cultured in a medium stimulating outgrowth of mesenchymal cells; whereas the cultured cells in series B were of epithelial morphology. Series A was further subdivided into three different age groups (≤15 years, 16–59 years, and ≥60 years) of non-SCC patients and one SCC group. Series B was composed of two groups; one with and one without SCC. Among the non-SCC patients in series A, there was an increase with age in the frequency of cells/sample with numerical and structural chromosomal changes as well as in the incidence of clonal chromosomal aberrations. No differences could, however, be detected between cancer patients and age-matched controls. In series B, the frequency of cells/sample with numerical changes and the incidence of clonal numerical aberrations were significantly higher among SCC patients. Three main conclusions could be drawn. First, the frequencies of clonal and non-clonal chromosome aberrations in UAT mucosa were age dependent. Second, the cytogenetic support for the validity of the field cancerization hypothesis was restricted to increased levels of numerical chromosome changes in epithelial cell cultures from cancer patients. Third, clonal chromosome aberrations, including autosomal and sex chromosome aneuploidies as well as structural rearrangements, are not restricted to neoplastic mucosal cells.

Clonal chromosome aberrations accumulate with age in upper aerodigestive tract mucosa

Abstract Short-term cultured non-neoplastic upper aerodigestive tract (UAT) mucosa samples from 36 patients with squamous cell carcinoma of the head and neck (SCC) and 53 patients with benign UAT disorders were cytogenetically analyzed. The cell cultures were divided into two series: in series A, cells were cultured in a medium stimulating outgrowth of mesenchymal cells; whereas the cultured cells in series B were of epithelial morphology. Series A was further subdivided into three different age groups (≤15 years, 16–59 years, and ≥60 years) of non-SCC patients and one SCC group. Series B was composed of two groups; one with and one without SCC. Among the non-SCC patients in series A, there was an increase with age in the frequency of cells/sample with numerical and structural chromosomal changes as well as in the incidence of clonal chromosomal aberrations. No differences could, however, be detected between cancer patients and age-matched controls. In series B, the frequency of cells/sample with numerical changes and the incidence of clonal numerical aberrations were significantly higher among SCC patients. Three main conclusions could be drawn. First, the frequencies of clonal and non-clonal chromosome aberrations in UAT mucosa were age dependent. Second, the cytogenetic support for the validity of the field cancerization hypothesis was restricted to increased levels of numerical chromosome changes in epithelial cell cultures from cancer patients. Third, clonal chromosome aberrations, including autosomal and sex chromosome aneuploidies as well as structural rearrangements, are not restricted to neoplastic mucosal cells.