Arzu Yaren

Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis

In non‐small‐cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl‐2 genes which are important in apoptosis and c‐kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival.

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors.

The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.

Angiotensin-Converting Enzyme Gene Polymorphism Is Associated with Anemia in Non–Small-Cell Lung Cancer

The angiotensin-converting enzyme (ACE) plays an important role not only in the regulation of vascular homeostasis but also in stimulation of hematopoiesis. We aimed to evaluate the association between insertion/deletion (I/D) polymorphism of the ACE gene and anemia at the time of the diagnosis. We enrolled 75 patients with non–small-cell lung cancer (NSCLC) and 85 age- and sex-matched healthy control participants. The I/D polymorphism of ACE was identified by using polymerase chain reaction from peripheral blood samples. Statistical analyses were performed with SPSS for Windows. The distributions of the ACE genotypes and alleles are similar in patients and in healthy participants (P = 0.29 and P = 0.08, respectively). In patients with NSCLC, 34 (45.3%) had anemia; of whom 3 (8.8%) had genotype II, 24 (70.6%) had genotype ID, and 7 (20.6%) had genotype DD (P = 0.001). The patients with the II and ID genotypes had more frequent anemia at the time of the diagnosis (odds ratio = 6.02; P = 0.001). Our findings suggest that I/D polymorphism of the ACE gene may influence the development of anemia in patients with NSCLC.

Utility of serum DNA and pyrosequencing for the detection of EGFR mutations in non-small cell lung cancer.

Mutations in the EGFR gene are critical determinants of treatment with EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) patients. DNA isolation from tumor samples usually requires surgery; therefore, we wanted to isolate DNA from circulating tumor cells by using the serum of NSCLC patients. This protocol was recently published. DNA was isolated from the serum of 52 Turkish NSCLC patients and their EGFR mutation status was examined by pyrosequencing. EGFR mutations were detected in 25 of the 52 patients (48.1%): 17 patients with delE746-A750, 2 with delE747-A750insP, and 6 with L858R. All mutations detected by pyrosequencing were confirmed by dideoxy sequencing, and the presence of the same mutations in the tumors was verified by using paraffin embedded tissues of all the patients. Mutations were detected more frequently in adenocarcinomas (24 of 36, 66.7%) than in squamous cell carcinomas (1 of 16, 6.3%) (P<0.001). These results confirm the utility of serum DNA and pyrosequencing for the detection of EGFR mutations in patients with advanced NSCLC.

Gemcitabine Combined with Infusional 5-Fluorouracil and High-Dose Leucovorin for the Treatment of Advanced Carcinoma of the Pancreas

Background: 5-Fluorouracil (5-FU) and gemcitabine are the major active drugs in the treatment of pancreatic cancer. Methods: Twenty-two patients with advanced pancreas cancer were treated with a new chemotherapy regimen consisting of infusional 5-FU and high-dose leucovorin with gemcitabine (GEMFUFOL). Results: A total of 200 cycles of chemotherapy were administered. The response rate was 27.3%, all responses being partial. The median survival time and 1-year survival rate were, respectively, 13 months and 60.4%. The toxicity was very low and severe hematological toxicity was exceptional. Conclusion: The GEMFUFOL regimen can be an active regimen for the treatment of advanced pancreatic cancer and has a low toxicity.

MDR1 single nucleotide polymorphism C3435T in Turkish patients with non-small-cell lung cancer.

We assessed whether single nucleotide polymorphisms (SNPs) in MDR1 gene C3435T predicted the outcome of platinum-based chemotherapies and survival in our non small cell lung cancer (NSCLC) patients. A total of 79 non-small cell lung cancer patients were enrolled to study. We determined the MDR1 C3435T single nucleotide gene polymorphisms. Median age was 60years: 91.7% male, 8.9% female. We found that CC, CT, TT genotype and T, C allele frequencies in lung cancer patients as 24.1%, 62%, 13.9% and 44.3%, 55.7%, respectively. Patients with CT genotype had a higher response rate (11.4%) than the other genotypes. However, this difference is not statistically significant (p=0.743). Cox regression analysis for overall survival showed that ECOG PS status 0 (HR PS 1 vs. 0, 5.68 p=0.002; HR of PS 2 vs. 0 is 21.579, p=0.001; HR of PS 3 vs. 0 is 35.35, p=0.001), stage ≤II (HR of stage III vs. I+II is 17.77; p=0.016, HR of stage IV vs. I+II is 26.97, p=0.006), and albumin level ≥3g/dl (HR of albumin <3g/dl vs. ≥3g/dl is 2.46, p=0.044) were the most important prognostic factors (also, time to progression was related to these factors). There was no significant association between the genotypes and clinicopathologic parameters; however, good performance status, early stage and ≥3g/dl albumin level were found to be the most important prognostic factors for overall survival and progression-free survival.

PRIMARY NEUROENDOCRINE CARCINOMA OF THE BREAST: A CASE REPORT

Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We present our experience of primary neuroendocrine carcinoma of the breast in a 76-year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the chest and abdomen showed no lesion for metastasis or another primary origin. Adjuvant hormone therapy was given, since the tumor was immunohistochemically receptor positive.

Insulin-like growth factor I (Igf-1) gene polymorphism in patients with non-metastatic breast cancer

We aimed to assess the association between IGF-I gene (CA repeats) polymorphism in breast cancer patients and their clinicopathological features, as well as disease recurrence and survival. Seventy-six non-metastatic breast cancer patients were enrolled in the present study. The IGF-I (CA) repeats were studied with polymerase chain reaction by using proper primers belonging to these gene areas from DNA samples. Results show that the non 19- non 19 homozygote were more common in patients without lymph node involvement (p=0.04), with low histological grade (p=0.04), with positive hormone receptor status (p=0.01), and in patients without recurrence (p=0.06). These results suggest that the non 19-non 19 carriers have some favorable prognostic factors, and IGF-I gene polymorphism (CA repeats) may affect disease recurrence and overall survival.

Secondary involvement of the breast in T-cell non-Hodgkin lymphoma, an unusual example mimicking inflammatory breast carcinoma

Non-Hodgkin lymphoma of the breast is a rare malignancy and present with almost equal frequency either as a primary or a secondary disease. Survival is poor in most cases of secondary breast lymphoma because of their advanced stage. We report a 35-year-old woman presenting with dyspnea as well as swelling, tenderness, and ruddiness in the left breast with non-cyclic pain for several months and maculopapular skin eruption in the same breast. Physical examination revealed fixed lymphadenopathies in both axillary regions. Radiologic evaluations (bilateral mammaograpy and ultrasonography) showed skin thickening in the left breast, asymmetrical densities in both breasts, and confirmed lymphadenopathies in the axillary regions. Excisional biopsies were performed to the left axillary lymph nodes and the breast skin eruptions. The histologic and immunohistochemical features were diagnosed as an ALK (−) anaplastic large cell lymphoma. A Computed Tomography examination was performed for staging the lymphoma and then chemotherapy was started. Thirty months after the diagnosis, the patient is still alive with disease. Because of the presence of systemic symptoms such as skin involvement and generalized lymphadenopathies (mediastinal, axillary or cervical), T cell lymphoma cases with breast involvement could mimic the clinical presentation of inflammatory breast carcinoma. Pathologic examination is needed for the correct diagnosis.

Lower motor neuron disease associated with myelofibrosis

We present a patient who has signs pointing to the involvement of lower motor neurons and myelofibrosis. To our knowledge, unlike lymphoproliferative disorders, co-occurrence of myelofibrosis and lower motor neuron disease (MND) has not been reported so far. A 64-year-old male patient was admitted to our hospital with the complaint of painful cramps in his neck and forearms. On physical examination marked hepatomegaly and splenomegaly were found. On neurologic examination nasal quality of the voice and slight palatal weakness were detected. There were generalised slight weakness and atrophy in both proximal and distal muscle groups. Fasciculations were observed especially in forearm muscles and it was observed that he had been avoiding head movements because of painful muscle cramps. Deep tendon reflexes were hypoactive. Nerve conduction studies were normal. By needle electromyography, giant motor unit action potentials (amplitudes up to 8 mV), fibrillation potentials, positive sharp waves and fasciculation potentials were detected in all muscles which were investigated. A hypercellular bone marrow (100%) was determined by bone marrow biopsy. In addition to increased production of the myeloid and megakaryocytic lines, abnormal aggregation and grouping of megakaryocytes were seen. Reticular fibers were increased. He had some benefit of dyphenilhydantoin treatment given for the painful cramps in his neck and forearm muscles. Hydroxyurea treatment was started for myelofibrosis. Six months later, his general condition was better, and the painful cramps were completely resolved. No marked deterioration has been detected in neurologic examination and electromyography for 1 year.