Rosai-Dorfman disease as a rare cause of cervical lymphadenopathy - case report and literature review.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, benign clinical entity of unknown cause. RDD is characterised by the overproduction and accumulation of histiocytes, primarily in the lymph nodes, although it may affect every organ and system. It predominantly affects children and young adults. Typically, patients are in good general condition, with massive cervical lymphadenopathy and fever. In about 40% of cases extranodal localisation of RDD is diagnosed. In laboratory tests the most common abnormalities are increased erythrocyte sedimentation rate (ESR), leukocytosis with neutrophilia, normocytic anaemia, and hypergammaglobulinaemia. Histopathological examination remains the mainstay of diagnosis - lymph nodes have massive sinusoidal dilation, containing histiocytes positive for S-100 and CD68, and negative for CD1a. Most patients do not require treatment as spontaneous remissions are observed. We present a brief review of the literature and the case of a six-year-old boy with cervical lymphadenopathy diagnosed with RDD. So far, the patient has not required systemic treatment and has been kept under observation.

Multifocal Extra-Adrenal Paraganglioma - Case Report.

Paraganglioma is a rare neoplasm originating from extra-adrenal pheochromocytes of the sympathetic and parasympathetic nervous system. It is usually benign and the treatment method of choice is a complete resection of the tumour. The authors present a case of 66-year-old female patient with a multifocal benign retroperitoneal paraganglioma, which was completely removed during surgery.

Morphological alterations in the tympanic membrane affected by tympanosclerosis: ultrastructural study.

The ultrastructure of tympanoslerotic tissue, surgically excised from patients, has been studied with particular reference to the morphological changes of the connective tissue components and mineralization. Detailed analysis revealed the combination of degenerative and fibroplastic alterations, especially in the circular fibrous layer of the thickened lamina propria. In the biological material in this study the authors recognized different stages of calcium plaque development with discrete, moderate, and severe degree of mineralization. Extracellular matrix vesicles, with or without calcareous deposits, released by degenerating fibroblasts were prominent. In these biopsies no distinct morphological features of an inflammatory reaction were seen.

Main histologic types of non-small-cell lung cancer differ in expression of prognosis-related genes.

BACKGROUND: There is increasing evidence that suggests that particular histopathologic types of non-small-cell lung cancer (NSCLC) display distinct molecular characteristics. We analyzed, in lung squamous cell carcinoma (SCC) and adenocarcinoma (AC), the expression of 8 genes that constitute 2 previously reported prognostic expression signatures in NSCLC. METHODS: Fresh-frozen tumor and normal lung samples were obtained at surgery from 135 patients with stage I-III NSCLC (89 (65.9%) SCC, 46 (34.1%) AC). Expression of CSF1 (colony stimulating factor for macrophages), carbonic anhydrase 9 (CA9), epithelial growth factor receptor (EGFR), dual specificity phosphatase 6 (DUSP6), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), monocyte to macrophage differentiation-associated (MMD), lymphocyte-specific protein tyrosine kinase (LCK) and signal transducer and activator of transcription 1 (STAT1) was assessed in SCC, AC, and in normal lung by quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR). Metastasis-free survival was analyzed according to the median value of gene expression in the entire NSCLC cohort and separately in SCC and AC. RESULTS: Expression of CA9, CSF1, DUSP6, STAT1, and MMD differed between NSCLC and normal lung. EGFR was more abundant in SCC compared with AC, whereas the reverse was true for DUSP6 and ERBB3. A high expression of CSF1 correlated with shorter metastasis-free survival in the entire NSCLC group (P = .016) and in SCC (P = .049) and AC (P = .034) cohorts. CONCLUSIONS: Several genes considered prognostic in NSCLC showed significantly different expression in SCC and AC, and thus should be analyzed separately in these 2 subtypes for their prognostic significance. CSF1 is similarly expressed in SCC and AC, and portends a poor outcome in the entire group of patients with NSCLC, and in SCC and AC when considered separately.

[Surgical treatment results of acquired external auditory canal atresia]. / Wyniki leczenia chirurgicznego nabytego zarosniecia przewodu sluchowego zewnetrznego.

UNLABELLED: Acquired post inflammatory external auditory canal atresia is a rear complication of external ear disease. It is presented as a connective tissue scar in bony part of external auditory canal. The aim of this study is clinical and epidemiological analysis and presentation of diagnostics and treatment results of patients with atresia treated in the Otolaryngology Department of Medical University of Gdansk. MATERIAL AND METHODS: In the period of 3 years (2008-11) 10 patients (8 women and 2 men) aged 30 to 70-years-old (medium 53 years) were treated for acquired atresia. All of these patients had medial closure of EAC with thick connective tissue scar and tympanic membrane involvement. Intrameatal access was performed in 5 patients, intraural access in 3 patients and retroaurical access in 2 patients. In all cases canaloplasty with meato-tympanic angle enlargement was performed, skin defect was replaced with free epidermal flap, silicon foil with fibrinous sponge was used for coverage. RESULTS: In all of our patients external auditory canal widening and hearing improvement was achieved. Due to increasing EAC narrowing four patients underwent second surgery with another free epidermal flap grafting. CONCLUSION: The selection of surgical access in patients with acquired atresia should comply with the etiology of the disease and the shape of EAC. During surgery we aim at maximal broadening of the bony part of EAC. The success of the treatment depends on meato-tympanic angle enlargement and free epidermal flap grafting.

[Diagnosis and treatment preauricular fistulas in children]. / Rozpoznawanie i leczenie przetok przedusznych u dzieci.

INTRODUCTION: Preauricular fistulas are not uncommon congenital disorders in children. They are associated with imperfect auricle formation as a consequence of incomplete fusion of the auditory hillocks of the first and second branchial arches. AIM: The aim of this study was to present diagnostic methods with evaluation of treatment results of preauricular fistulas in children. MATERIALS AND METHODS: We analysed retrospectively clinical and epidemiological features, diagnostic methods and treatment results of the patients with preauricular fistula attended in the Otolaryngology Department of Medical University in Gdansk. RESULTS: Between 1995 and 2009 in the Department of Otolaryngology MGUed 23 children (13 girls and 10 boys) were treated for preauricular fistulas. The age of the children ranged between 2 to 16 years (median 7.7). The fistula was recognized on the left side in 14 children, in 6 on the right and bilaterally in 3 children. The diagnosis was based on the presence of a cutaneous fistula in the region of the helix's anterior crus with inflamed surrounding and purulent discharged in physical examination and in radiological imaging (MRI). Patients were treated surgically in the classical way and using Prasada's method including resection of the cutaneous fistula and cyst with a part of the helix. Squamous epithelium in the resected fistulas was found in 91.3% of the children. No recurrence was observed, good cosmetic outcome was achieved in all children. CONCLUSIONS: Each patient with bilateral preauricular fistula needs to be diagnosed for congenital disorders of the middle ear and kidneys. MRI may be useful in establishing the location of the fistula. Surgical treatment is not necessary in preauricular, blind-ended sinuses. In the postoperative material of the sinus squamous epithelium is found.

[A case of maxillary sinus carcinoma of a 24-year-old man, holistic aspects of care]. / Rak zatoki szczekowej u 24-letniego mezczyzny, aspekty opieki holistycznej.

The aim of this study is to report a carcinoma affecting the maxillary sinus of a 24-years old man. Malignant tumors of the nasal cavity and paranasal sinuses are rare and a very heterogeneous group of tumors. The most common is a squamous cell carcinoma. Sinonasal malignances usually present as a difficult diagnostic and therapeutic problem. The treatment depended on location, extension and histology of the tumor, clinical condition and the patient desire. It consisted of surgery, RT, surgery and postoperatory R, and concurrent QT and RT. The treatment should be assessed individually for each patient. The treatment of patients with paranasal neoplasms requires a multidisciplinary cooperation. High quality care requires the preparation of a team of professionals dedicated to their work. We observe generally human trends to restore well being in difficult situation. Patients transform the information about them or change the values system. Psychooncological help in this field reinforces natural mechanism of restoring well being, increasing positive emotions and patient's own activity.

Malignant germ cell tumors associated with Swyer syndrome.

Swyer syndrome is characterized by a higher risk of developing genital malignancies. In this disorder, the most common is gonadoblastoma and dysgerminoma but also, in rare cases, choriocarcinoma. The prognosis in choriocarcinoma is poor. The early diagnosis of dysgenetic gonads is necessary in view of the risk of malignancies. It can be difficult due to its different clinical masks. When the neoplasm precedes the diagnosis of gonadal dysgenesis, adequate oncological treatment should be introduced with parallel gonadectomy. We present a case of 14-year-old female with 46, XY karyotype with choriocarcinoma in one gonad and dysgerminoma in the second one.

[Molecular control of bone resorption in chronic otitis media with cholesteatoma]. / Regulacje molekularne procesu niszczenia kosci w zapaleniu perlakowym ucha.

UNLABELLED: Bone destruction in chronic otitis media with cholesteatoma is a common phenomenon. Expanding growth of cholesteatoma in the middle ear causes ischemia of the mucosa and bones with granulation tissue production. THE AIM OF THIS STUDY: was to assess the expression and distribution of the key regulators of bone destruction: osteoprotegerin (OPG), Receptor Activator for Nuclear Factor kappa B Ligand (RANKL) and tumour necrosis factor alpha (TNF-alpha) in chronic otitis media with cholesteatoma and their role in the pathomechanism of bone resorption. MATERIAL AND METHODS: We performed immunohistochemical study of the cholesteatoma tissue collected from 21 patients suffering from chronic otitis media with cholesteatoma and 16 samples of normal external auditory meatal skin. This material was analysed histopathologically and by means of immunoperoxidase immunohistochemical technique with the use of antibodies against OPG, RANKL and TNF-alpha and their quantitive evaluation. RESULTS: In all patients with cholesteatoma, features of auditory ossicles and temporal bone destruction were demonstrated. We found that cholesteatoma and granulation tissue cells release factors of the OPG/ RANKL/RANK system and TNF-alpha. In cholestatoma a higher expression of RANKL, OPG and TNF-alpha positive was demonstrated when comparing to the skin of external auditory meatus. These factors were relatively higher expressed in the stroma rather than in the epithelium of cholesteatoma. RANKL-positive cells were demonstrated mainly in the stroma cells, whereas OPG-positive ones in the cholesteatoma epithelium. The reaction with the antibodies against OPG, RANKL and TNF-alpha was weak in the external auditory meatal skin. CONCLUSIONS: Bone destruction in chronic otitis media with cholesteatoma is a common process dependent on osteoclast activating factors. OPG/ RANKL/RANK system and TNF-alpha play a key role in the process of osteolysis in otitis media with cholesteatoma. We found no positive correlation between bone destruction advancement and the level of examinated proteins.

Analysis of PI3K/AKT/mTOR signalling pathway in high risk neuroblastic tumours.

Neuroblastoma (NB) represents one of the most common paediatric tumours. Despite advance in NB research and treatment, the outcome of the patients from the high-risk group remains poor. PI3K/AKT/mTOR signalling pathway which is involved in oncogenesis and cancer progression of many tumours, in parallel constitutes the target for the biologically based oncological therapy. In this study we analyzed the status of PI3K/AKT/mTOR signalling route in the primary tumour tissue samples from a group of 39 high-risk NB. The pathway activation state was assessed immunohistochemically using antibodies with specificity towards PI3Kp85, PI3Kp110, phospho-AKT, phospho-mTOR, phospho-p70S6K and phospho-4EBP1. Moreover, expression of PTEN, bcl2 and cyclin D1 was examined. We found that most of tumours were positive for PI3Kp85 and PI3Kp110, as well as for p-AKT, p-mTOR and its downstream effectors p-p70S6K and p-4EBPI. PTEN was expressed in all cases, bcl2 and cyclin D1 staining was found in more than 90% of examined NB. Statistical analysis revealed that p-AKT expression was correlated with p-mTOR and strong cyclin D1 labelling. Furthermore, high expression of p-4EBP1 was significantly associated with p-p70S6K expression, high cyclin D1 and lower differentiation of the tumour. PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk NB and it seems that this group of patients may benefit from targeted therapy with kinase inhibitors.

[Osteomas and exostoses of external auditory canal in material of Otolaryngology Department Medical University of Gdansk]. / Kostniaki i wyrosla kostne przewodu sluchowego zewnetrznego w materiale Kliniki Otolaryngologii Gdanskiego Uniwersytetu Medycznego.

INTRODUCTION: Osteomas and exostoses of the external auditory canal are benign tumours arising in bones, leading to its obstruction and causing hearing loss. The treatment of these entities may present a therapeutic dilemma. AIM OF THE STUDY: To assess epidemiological and clinical data and surgical treatment effectiveness. SUBJECTS AND METHODS: The study group consisted of 21 patients (14 men and 7 women) between 18 to 63 years of age, treated in the Otorhinolaryngology Department of Medical University of Gdansk from 1995 to 2009. The results of audiometric, radiological and histopathological examination were taken into consideration. RESULTS: Unilateral osteomas developing in tympanosquamous suture in 5 patients, in tympanomastoid suture in 4. Bilateral exostoses occured in 12 patients in anterior, posterior and inferior wall of the external auditory canal. In all patients: conductive hearing loss ranged from 15 to 30 dB (average 29.9 dB), in 6 patients with concomitant sensorineural component. Osteomas were removed via intrauricular approach according to Mawson-Goodhill's method. Exostoses were removed via intrauricular, intracanal or postauricular approach. Histological examination confirmed benign overgrowth of compact and trabecular bone. The auditory canal was successfully reamed, the hearing improved in all patients. CONCLUSIONS: Osteomas are benign tumours leading to obstruction of the external auditory canal. Exostosis is the overgrowth of the external auditory canal's compact bone in adults. Osteomas and exostoses may lead to hearing loss. Indications to surgical treatment are ear pain, progressive hearing loss and recurrent otitis external.

Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung.

PURPOSE: Adjuvant treatment may improve survival in early-stage squamous cell carcinoma (SCC) of the lung; however, the absolute gain is modest and mainly limited to stage II-IIIA. Current staging methods are imprecise indications of prognosis, but high-risk patients can be identified by gene expression profiling and considered for adjuvant therapy. EXPERIMENTAL DESIGN: The expression of 29 genes was assessed by reverse transcriptase quantitative PCR in frozen primary tumor specimens obtained from 66 SCC patients who had undergone surgical resection. Expression values were dichotomized using the median as a cutoff value. We used a risk score to develop a gene expression model for the prediction of survival. RESULTS: The univariate analysis of gene expression in the training cohort identified 10 genes with significant prognostic value: CSF1, EGFR, CA IX, PH4, KIAA0974, ANLN, VEGFC, NTRK1, FN1, and INR1. In the multivariate Cox model, CSF1 (hazard ratio, 3.5; P = 0.005), EGFR (hazard ratio, 2.7; P = 0.02), CA IX (hazard ratio, 0.2; P < 0.0001), and tumor size >4 cm (hazard ratio, 2.7; P = 0.02) emerged as significant markers for survival. The high prognostic value of a risk score based on the expression of the three genes (CSF1, EGFR, and CA IX) was positively validated in a separate cohort of 26 patients in an independent laboratory (P = 0.05). CONCLUSIONS: The three-gene signature is strongly associated with prognosis in early-stage SCC. Positive independent validation suggests its suitability for selecting SCC patients with an increased risk of death who might benefit from adjuvant treatment.

BRCA1: a novel prognostic factor in resected non-small-cell lung cancer.

BACKGROUND: Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1). METHODOLOGY AND PRINCIPAL FINDINGS: We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04). CONCLUSIONS: Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated.

Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients.

BACKGROUND: Sentinel lymph node identification has been tested in lung cancer patients with conflicting results. The present study was designed to assess the sensitivity, negative predictive value, and accuracy of intraoperative sentinel lymph node mapping by means of a radio-guided method in patients with nonsmall cell lung cancer to find the most appropriate definition of sentinel lymph node and to evaluate the usefulness of different particle sizes of radiocolloid. METHODS: One hundred ten patients with clinically N0 nonsmall cell lung cancer were enrolled in the pilot study of intraoperative sentinel node identification. Four quadrants of the peritumoral tissue were injected with 2 mL of 0.5 mCi technetium-99m suspension. Four radiocolloids of different particle size were used. After complete lymphadenectomy, all resected lymph nodes were examined with hematoxylin-eosin staining. All sentinel nodes negative for metastases by routine staining were searched further for metastatic deposits with both serial sections and immunohistochemistry for cytokeratins. RESULTS: The radio-guided method had a high identification rate, a high sensitivity, and a high negative predictive value (100%, 87%, and 93%, respectively) when immunohistochemistry was considered. When standard hematoxylin and eosin staining was applied, sensitivity and negative predictive value of sentinel lymph node labeling was lower (74% and 89%, respectively). No significant differences were found in either the sensitivity or negative predictive value among the colloid solutions of different particle size used in radio labeling, although smaller particles have shown a tendency to produce better results. CONCLUSIONS: The radio-guided technique provides efficient sentinel lymph node identification in lung cancer. Further studies are warranted to confirm the clinical utility of this strategy.

Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism.

The aim of this study was to assess whether the TP53 Arg72Pro polymorphism is associated with an increased risk of non-small cell lung cancer (NSCLC). Additionally, in NSCLC patients, we investigated a potential association between this polymorphism and somatic TP53 gene mutations in tumour cells. The study group included 240 NSCLC patients who underwent curative pulmonary resection. The control group (576 healthy subjects) was matched for sex and cigarette smoking. TP53 Arg72Pro polymorphism was determined by denaturing high-performance liquid chromatography. Tumours from 157 NSCLC patients were analysed for mutation in TP53 exons 5-8 by single strand conformation polymorphism, followed by sequencing of samples with different band pattern. Tumours from the remaining 83 patients were subjected to a direct sequencing of TP53 exons 5-8. The proportion of Pro homo/heterozygotes versus Arg homozygotes was significantly higher in NSCLC patients (54%) than in controls (46%, p = 0.034). The crude odds ratio for NSCLC development in Pro72 allele carriers was 1.39 (95% CI: 1.03-1.88). When adjusted for sex, age and smoking status in the multivariate logistic regression model, odds ratio for NSCLC development was 1.28 (95% CI: 0.91-1.80). Somatic TP53 mutations were found in 62 out of 240 NSCLC patients (26%), more frequently in Pro carriers (31%) than in Arg homozygotes (20%, p = 0.06). These results indicate that the TP53 codon 72 Pro allele may increase the risk of NSCLC. Additionally, the correlation between Pro72 and somatic TP53 mutations suggests that Pro72 allele carriers may be predisposed to tumour development along a p53 associated form of NSCLC, a finding that warrants further investigations.

Coexistence of hepatocellular carcinoma and gastrointestinal stromal tumor: a case report.

Malignant gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors originating from the wall of the gastrointestinal tract. Their coexistence with other tumors originating from other germ layers is unique. We have reported a case of a 63-year-old GIST patient presenting as an epigastric mass associated with hepatic tumor. Histologically, the mesenteric tumor was composed of spindle cells showing both neural and smooth muscle differentiation. Immunohistochemical examination showed positive staining for CD117, vimentin, S-100, and SMA, while CD34 antigen was negative. The hepatic tumor was diagnosed as hepatocellular carcinoma (HCC). To the best of our knowledge, this is the first case of GIST and HCC coexistence. The rarity of the case, however, should not lead to ignoring such a possibility in differential diagnosis.

[Problems of nephroblastoma therapy in children with chronic renal failure--report of two cases]. / Problemy leczenia nerczaka zarodkowego u dzieci z przewlela niewydolnoscia nerek--opis dwóch przypadków.

UNLABELLED: Chronic renal failure (CRF) in children with nephroblastoma occurs in less than 4% of cases. THE AIM of the study was to present the diagnostic and therapeutic difficulties in two children with nephroblastoma in whom chemotherapy was conducted in the phase of CRF. MATERIAL AND METHODS: 52 children with nephroblastoma were treated in the Department of Paediatrics, Haematology, Oncology and Endocrinology, Medical University of Gdansk, between 1992 and 2004. Chronic renal failure occurred in two of them. In one patient (case 1) CRF was associated with a congenital complex urinary tract defect (cystic dysplasia of the left kidney, megaureter and bilateral hydronephrosis), in the second one (case 2), CRF resulted from bilateral nephrectomy in the course of relapsing bilateral nephroblastoma. CONCLUSIONS: Chemotherapy in children with CRF is a serious therapeutical dilemma. The effective dose of the cytotoxic drug, the time of its administration and the periods between the chemotherapy cycles are very difficult to assess for this group of patients. Problems also occur with the achievement of proper energy intake and good physical development of the child.

Karyotypic characterization of 64 nonmalignant thyroid goiters.

Cytogenetic analyses were performed on 64 nonmalignant thyroid goiters (11 common and 53 multinodular goiters) after short-term culture. The majority of goiters (67%) were characterized by a normal karyotype, but in 5 common (45%) and 16 nodular (30%) goiters, small clones with various numerical and/or structural aberrations were found, in addition to many normal cells. Trisomy or tetrasomy 7 was the most frequent numerical aberration, seen in five cases. Deletion of 18p11 was found in four cases, and in three of them as the sole change. Selection and clonal evolution of aneuploid cells present in nonmalignant goiters could underlie progression into adenoma formation.

[Analysis of prognostic value of TP53 gene mutations in non-small cell lung cancer]. / Analiza rokowniczego znaczenia mutacji genu TP53 u chorych na niedrobnokomórkowego raka pluca.

The aim of this study was to assess the frequency and prognostic value of TP53 gene somatic mutations in non-small cell lung cancer. The study group included 240 NSCLC patients who underwent pulmonary resection at the Department of Thoracic Surgery, Medical University of Gdansk. Tumour samples were evaluated for the presence of TP53 gene mutations in exons 5-8. In 157 cases SSCP method was used as a screening followed by sequencing of positive samples. In the remaining 83 patients mutations were analysed by direct sequencing. A total of 76 mutations (32%) were found, of those a missense type was dominant (67%), followed by silent and null type mutations (14% and 10%, respectively). There was no correlation between mutations and clinical characteristics, including age, sex, histological subtype, differentiation, tumour size, lymph node metastases, pTNM stage and smoking status. A multivariate Cox analysis demonstrated that tumour differentiation and pTNM stage were independent prognostic factors, whereas TP53 gene mutations were not. The results of this study indicate that TP53 gene mutations in NSCLC patients are not correlated with clinical characteristics and have no impact on survival.

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the occurrence of MDM2 amplification in surgically treated NSCLC patients. Molecular data were correlated with clinicopathological factors and evaluated for their prognostic value. The study group included 116 NSCLC patients who underwent pulmonary resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR using hybridization probe format on a LightCycler (Roche). The calculated ratio was a MDM2 value normalized to the amplification of the housekeeping gene phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan-Meier method and compared with the use of the log-rank test. Multivariate analysis was based on Cox regression analysis. MDM2 amplification was found in 24 patients (21%). There was no relationship between MDM2 amplification and clinicopathological factors, such as sex, age and stage of disease, pT, pN, histology and tumor differentiation. Median disease-free survival (DFS) in patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS 24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival (OS) in patients with and without MDM2 amplification was 9 and 33 months, respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The strong prognostic relevance of MDM2 amplification for both DFS and OS was confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results suggest that MDM2 gene amplification analysis provides additional prognostic information in surgically treated NSCLC patients.