Eosinophilia is a favourable prognostic marker in oral squamous cell carcinoma

Suusyöpä on yleisin pään ja kaulan alueen pahanlaatuisista kasvaimista. Niistä yli 90 % on levyepiteelikarsinoomia. Koska suusyöpäpotilaan viisivuotisennuste on vain noin 50 %, on jatkuva tarve löytää keinoja ennustamaan potilaan selviytymistä ja ohjaamaan hoitoa. Suun levyepiteelikarsinooman ympäristössä havaitaan säännöllisesti eosinofiilejä. Eosinofiili on ihmisen immuunijärjestelmän erikoistunut solu, joiden määrä lisääntyy sekä tulehdusreaktioissa että syöpien läheisyydessä. Toistaiseksi ei tiedetä, miten eosinofiilit liittyvät suun levyepiteelikarsinoomaan, mutta oletuksena on, että suusyöpään liittyvällä eosinofilialla, TATE (tumor-associated tissue eosinophilia), voisi olla vaikutusta suun levyepiteelikarsinoomapotilaan ennusteeseen. Tämän tutkimuksen tarkoituksena oli selvittää TATE:n ilmenemistä ja vaikutusta potilaan ennusteeseen suun levyepiteelikarsinoomassa. Lisäksi tutkimus käsittelee potilaan ennusteen kannalta optimaalista eosinofiilimäärän raja-arvoa, jota voitaisiin käyttää patologin työkaluna ennusteen arvioinnissa. Tutkimusaineisto koostui Turun yliopiston Suupatologian laitoksella vuosina 2002-2010 tutkituista 122 suuontelon ja huulen limakalvokoepalasta, jotka oli otettu diagnostisia tarkoituksia varten 99 potilaalta. Tutkimuksen potilaista 44 oli naisia ja 55 miehiä, ja heidän keski-ikänsä oli 65,3 vuotta. Seuranta-aika oli keskimäärin 40,7 kk. Kaksi tutkijaa analysoivat hematoksyliini-eosiinilla värjätyt näytteet suurentamalla ne 400-kertaisiksi valomikroskoopilla. Eosinofiilien määrä laskettiin yhteensä kuudelta edustavimmalta syövän ja strooman alueelta. TATE:n suhde potilaan kliinispatologisiin piirteisiin ja selviytymiseen selvitettiin Turun yliopistollisen keskussairaalan potilastiedoistoista ja analysoitiin tilastollisesti käyttämällä Fischerin testiä. Työllä oli Varsinais-Suomen sairaanhoitopiirin eettisen toimikunnan lupa (nro T10/2011, päätös O31/11). Levyepiteelikarsinooman kliininen kuva vaihteli haavaisen muutoksen ollessa yleisin. Yleisin sijainti levyepiteelikarsinoomalle oli kieli. TATE:a löydettiin 61,5 %:sta (78/122) levyepiteelikarsinoomanäytteitä. Mikäli TATE:a ei löydetty tai sen määrä oli korkea, oli potilaan selviytyminen tilastollisesti merkitsevästi parempi kuin potilailla, joilla TATE oli matala. Lisäanalyyseissä havaittiin, että potilaan ennuste oli tilastollisesti merkitsevästi huonompi, mikäli TATE:n raja-arvo oli vähemmän kuin neljä eosinofiiliä per tutkittu mikroskooppinäkymä (HPF). TATE on täten merkki suun levyepiteelikarsinoomapotilaan paremmasta ennusteesta erityisesti, kun havaitaan enemmän kuin neljä eosinofiiliä/HPF. Tutkimustulosten varmistamiseksi tarvitaan kuitenkin jatkossa laajempia tutkimuksia.

Squamous cell carcinoma of the renal pelvis with stones and inferior vena cava infiltration. Case report

We report a rare case of a 50 year old man with renal squamous cell carcinoma (SCC) who first came to our attention with renal colic and fever not responding to antibiotic or analgesic treatment. He had a long history of kidney stones, but had not undergone any imaging in the last 5 years. Physical examination revealed tenderness and a palpable mass in the right flank and lumbar region. A whole body CT scan was performed, revealing an 11 cm mass in the right kidney infiltrating the inferior vena cava. There were areas of calcification within the mass and multiple stones within the renal pelvis. The tumor was considered unsuitable for resection according to radiological and clinical criteria. The mass was biopsied percutaneously under CT guidance and histological examination revealed squamous cell carcinoma of the renal pelvis. The patient was treated with neoadjuvant chemotherapy and embolization of the renal artery. He died one month after diagnosis. To our knowledge this is the second reported case in the world of renal SCC infiltrating the inferior vena cava and with kidney stones.

From genes to radioresistance in head and neck squamous cell carcinoma

Head and Neck Cancers (HNC) are a group of tumours located in the upper aero-digestive tract. Head and Neck Squamous Cell Carcinoma (HNSCC) represent about 90% of all HNC cases. It has been considered the sixth most malignant tumour worldwide and, despite clinical and technological advances, the five-year survival rate has not improved much in the last years. Nowadays, HNSCC is well established as a heterogeneous disease and that its development is due to accumulation of genetic events. Apart from the majority of the patients being diagnosed in an advanced stage, HNSCC is also a disease with poor therapeutic outcome. One of the therapeutic approaches is radiotherapy. However, this approach has different drawbacks like the radioresistance acquired by some tumour cells, leading to a worse prognosis. A major knowledge in radiation biology is imperative to improve this type of treatment and avoid late toxicities, maintaining patient quality of life in the subsequent years after treatment. Then, identification of genetic markers associated to radiotherapy response in patients and possible alterations in cells after radiotherapy are essential steps towards an improved diagnosis, higher survival rate and a better life quality. Not much is known about the radiation effects on cells, so, the principal aim of this study was to contribute to a more extensive knowledge about radiation treatment in HNSCC. For this, two commercial cell lines, HSC-3 and BICR-10, were used and characterized resorting to karyotyping, aCGH and MS-MLPA. These cell lines were submitted to different doses of irradiation and the resulting genetic and methylation alterations were evaluated. Our results showed a great difference in radiation response between the two cell lines, allowing the conclusion that HSC-3 was much more radiosensitive than BICR-10. Bearing this in mind, analysis of cell death, cell cycle and DNA damages was performed to try to elucidate the motifs behind this difference. The characterization of both cell lines allowed the confirmation that HSC-3 was derived from a metastatic tumour and the hypothesis that BICR-10 was derived from a dysplasia. Furthermore, this pilot study enabled the suggestion of some genetic and epigenetic alterations that cells suffer after radiation treatment. Additionally, it also allowed the association of some genetic characteristics that could be related to the differences in radiation response observable in this two cell lines. Taken together all of our results contribute to a better understanding of radiation effects on HNSCC allowing one further step towards the prediction of patients’ outcome, better choice of treatment approaches and ultimately a better quality of life.

Review: Head and neck squamous cell carcinoma in sub-Saharan Africa

Aim Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa. Methods Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed. Results Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare. Conclusions The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol.

Primary squamous cell carcinoma of the stomach presenting as a huge retroperitoneal tumor: a case report

A man complained of upper abdominal pain and early satiety for one month. An upper gastrointestinal endoscopy showed nothing special. A CT scan of the abdomen was performed, which demonstrated a huge heterogeneous retroperitoneal mass close to the dorsal wall of the stomach and surrounding the abdominal aortic and celiac trunk. The resected specimen suggested that an irregular tumor invaded the dorsal wall of the stomach. Postoperative histological examination confirmed that it was a gastric squamous cell carcinoma.

Expression of TIMP-2 in HPV-16 infected oral squamous cell carcinoma in patients in Iraq

Aim: To determine the expression of tissue inhibitors of metalloproteinases (TIMP-2) in oral squamous cell carcinoma (OSCC) and the difference in its expression level between positive and negative HPV-16 (human papilloma virus- 16) OSCC patients. Methods: This study was conducted on 33 biopsies obtained from patients with OSCC and 10 normal oral mucosa as controls. In situ hybridization (ISH) was used to investigate the presence of HPV-16, while immunohistochemistry (IHC) was used to estimate the expression level of TIMP-2. Results: The TIMP-2 was expressed in 27 (81.8%) of OSCC sections with no significant difference between its expression level in HPV-16 positive and HPV-16 negative OSCC cases (p=0.058). TIMP-2 was found to be highly expressed in OSCC sections, and the presence of HPV was not related to its overexpression. Conclusions: The percentage of samples that appeared to accommodate detectable HPV-16 was high, but no significant difference was observed in relation to TIMP-2 expression level. Future studies with a larger number of patients are highly recommended to address the possible association between TIMp-2 and OSCC positive HPV-16.

Contribution to the study of prognostic factors in canine oral squamous cell carcinoma

Tese de Doutoramento em Ciências Veterinárias, na Especialidade de Clínica

Cytogenetics of basal cell carcinoma and squamous cell carcinomas

Cytogenetic analysis is a powerful tool that allows analysis of chromosomal aberrations associated with diseased states. In particular, a combination of cytogenetic techniques has allowed the identification of aberrations associated with cancer development, including cancers of the skin. This chapter provides a comprehensive overview of cytogenetic alterations in basal and squamous cell carcinomas of the skin. These two distinct lesions have altered karyotypes that are consistent with their malignant potential. Basal cell carcinomas, although relatively stable lesions, are highly associated with recurrent aberrations of chromosomes 6, 7, 9 and X, as detected by a number of cytogenetic techniques. Squamous cell carcinomas, on the other hand are associated with a much higher degree of instability, involving aberrations of chromosomes 3, 7, 8, 11, 13, 17 and 18, as detected using a number of cytogenetic techniques. Overall, the numbers and types of aberrations associated with basal and squamous cell carcinoma, define the characteristic behaviour associated with these lesions and identification of these aberrations may aid in the understanding of malignant potential, prognosis and treatment of these skin cancers.

Distinct regions of loss of heterozygosity on 22q at different sites of head and neck squamous cell carcinomas

Background: Frequent loss of heterozygosity (LOH) has been reported in many types of cancer, including head and neck carcinomas. Somatic deletions involving specific chromosomal regions are strongly associated with inactivation of the allele of a tumor suppressor gene located within the deleted region. In most studies concerning LOH in head and neck squamous cell carcinomas (HNSCC) the different anatomical sites are not distinguished. The behavior of tumors arising at various sites differs significantly, however, suggesting different intrinsic tumor properties. In this study we compared the LOH on 22q and its relationship to clinicopathological parameters at the three major sites of HNSCC: oral cavity, larynx and pharynx. Material/Methods: LOH and microsatellite instability (MSI) were studied using seven polymorphic microsatellite markers mapped to the 22q11-q13.3 region in 37 oral, 32 laryngeal, and 31 pharyngeal carcinomas. Results: Two separate regions of LOH were identified in the laryngeal (22q11.2-12.1) and oral cavity (22q13.1-13.31) tumors. When the different anatomical sites were compared, a statistically significant difference was found between the presence of LOH at D22S421 (p<0.001), D22S315 (p=0.014) and D22S929 (p=0.026) in the laryngeal tumors. Conclusions: These data suggest that distinct regions on 22q are involved in LOH in oral cavity and laryngeal tumorigenesis but do not support a similar association between the development of pharyngeal tumors and genes located on 22q. These findings implicate the presence of different tumor suppressor genes mapping to distinct regions on chromosome 22q in oral and laryngeal carcinomas.

Regulation of squamous cell differentiation in human head and neck carcinoma cells by retinoids

Retinoids have been found to be effective in the prevention of premalignant lesions and second primary cancers in the upper aerodigestive tract. Further development of retinoids for prevention and therapy of head and neck squamous cell carcinoma (HNSCC) requires a better understanding of their mechanism of action on the growth and differentiation of such cells. I have chosen to employ cultured HNSCC cell lines as a model system for investigating the mechanism underlying the effects of retinoids. These cells are useful because all-trans retinoic acid (ATRA) inhibits their proliferation. Furthermore, two HNSCC cell lines were found to express three squamous differentiation (SqD) markers characteristic of normal keratinocytes and ATRA suppressed the expression of these markers as reported for normal keratinocytes. It is thought that nuclear retinoic acid receptors (RARs and RXRs), which act as DNA-binding transcription modulating factors, mediate the effects of retinoids on the growth and differentiation of normal and tumor cells. I found that all four cell lines examined expressed RAR-$\alpha ,$ RAR-$\tau ,$ and RXR-$\alpha$ and three of four expressed RAR-$\beta .$ ATRA treatment increased the level of RAR-$\alpha ,$ -$\beta ,$ and -$\tau$ in four cell lines. Two HNSCC cell lines that exhibited a progressive increase in the expression of SqD markers during growth in culture also showed a concurrent decrease in RAR-$\beta$ level. Moreover, increasing concentrations of RA suppressed the SqD marker while inducing RAR-$\beta$ mRNA. Several synthetic retinoids which exhibit a preference for binding to specific nuclear RARs showed a differential ability to inhibit cell proliferation, transactivate transcription of the reporter genes (CAT and luciferase) from the RA response element (RARE) of the RAR-$\beta$ gene, and induce RAR-$\beta$ expression. Those retinoids that were effective inducers of RAR-$\beta$ also suppressed SqD effectively, indicating an inverse relationship exists between the expression of RAR-$\beta$ and SqD. This inverse relationship suggests a role for RAR-$\beta$ in the suppression of SqD. ^