Daniela Kandioler-Eckersberger

The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.

BACKGROUND The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.

Contralateral breast cancer: molecular differentiation between metastasis and second primary cancer

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene. With this molecular approach, we were able to define the relationship within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading.In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

Minimal invasive Thoraxchirurgie

ZusammenfassungGrundlagen: Vor 10 Jahren hat man begonnen, die minimal invasive Methode auch in die Thoraxchirurgie einzuführen, und seither wurden schon beinahe alle thoraxchirurgischen Eingriffe mit dieser videoassistierten Technik (VATS) durchgeführt. So hat die thorakoskopische Chirurgie einen festen Stellenwert eingenommen. Methodik: Anhand der eigenen Erfahrungen und Berichte aus der Literatur wird versucht, den aktuellen Stand in bezug auf Indikation, Operationstechnik, Konversionsrate sowie Ausbildung darzulegen und mögliche Entwicklungen aufzuzeigen. Ergebnisse: Als gesicherte Indikationen sind aus heutiger Sicht anzusehen: Spontanpneumothoarax, Biopsie mediastinaler und pleuraler Prozesse und Raumforderungen, der periphere Rundherd der Lunge, Lungenbiopsie bei interstitiellen Gerüsterkrankungen, Lungenzysten und Emphysem, Sympathektomie, Perikardfenster, Pleurodese. Fraglich und nicht routinemäßig wird VATS angewendet zur: Dekortikation beim Empyem und Hämatothorax, Metastasektomie, Behandlung des Bronchuskarzinoms zur Lobektomie bzw. Pneumonektomie und bei malignen Erkrankungen des Oesophagus. Schlußfolgerungen: VATS gilt heute unumstritten als wertvolle Standardmethode in der Diagnostik und Therapie thorakaler Erkrankungen. Den tatsächlichen Vorteil gegenüber den offenen Methoden versucht man nun durch Vergleich von technischer Durchführbarkeit, Schmerzreduktion, Kosten-Nutzen-Analysen, Sicherheit und Risiko sowie die Anwendbarkeit in der Malignomchirurgie herauszuarbeiten.SummaryBackground: This year marks the tenth anniversary of the beginning of the new era of video-assisted thoracic surgery. During that time, nearly every type of thoracic surgical operation has been performed “through the scope”. Video-assisted technique (VATS) has taken a firm place in thoracic surgery. Methods: By means of available reports of the literature and personal experiences the current status is pointed out for indications, technical procedure, conversion rate as well as training and education to identify areas of potential development. Results: Nowadays commonly accepted indications include: Spontaneous pneumothorax, biopsies in pleural and mediastinal diseases or tumors, peripheral coin lesions, biopsies in interstitial lung diseases, cysts and emphysema, sympathectomy and pericardial windows. VATS is used not routinely in metastasectomy, decortication after empyema and hematothorax, treatment in lung cancer for lobectomy or pneumonectomy and in oncological esophageal surgery. Conclusions: In a wide field VATS has become a standard procedure in diagnosis and therapy. The debate between proponents of the thoracoscope and an open approach has largely focused on: technical feasibility, pain reduction, relative costs both procedural and in — patient, safety issues and the adequacy of resection in malignant diseases.

p53 Gen - Zukunftsperspektiven

SchlußfolgerungenBasierend auf unseren Labordaten wäre es durch eine prätherapeutische p53-Gen-Analyse in Zukunft möglich, Vorhersagen über das Ansprechen eines Lungentumors auf Chemotherapie/Radiotherapie zu treffen. Abgestimmt auf die biologischen Eigenheiten eines malignen Tumors wäre dadurch eine individuelle Behandlung jedes Patienten möglich, mit direkten Konsequenzen in bezug auf die Wahl des wirksamsten Cheomtherapeutikums, des besten Zeitpunktes für die Operation und nicht zuletzt auf das gezielte Vermeiden einer unwirksamen Therapie und den damit verbundenen Nebenwirkungen.