Yavuz Ozisik

Deletion 7q22 in uterine leiomyoma: A cytogenetic review

The cytogenetic patterns of uterine leiomyomas have been extensively investigated, and cases characterized by specific clonal changes have been documented in detail. In these tumors one of the cytogenetic changes frequently observed has been a del(7), particularly del(7)(q22), usually as a sole anomaly. This is confirmed by our experience and by reports in the literature. The fact that del(7) is one of the most common abnormalities in leiomyoma raises the question of its role in tumor development. The main purpose of this review is to analyze the above aspect and to interpret its possible meaning. Our findings on cytogenetic abnormalities of chromosome 7 in leiomyoma, together with those reported in the literature, are reviewed and discussed. A listing of the genes located at 7q22 is also presented.

Sonographic and Electrodiagnostic Evaluations in Patients With Aromatase Inhibitor-Related Arthralgia

PURPOSE To investigate the prevalence of arthralgia in breast cancer patients taking aromatase inhibitors (AIs) and perform a detailed rheumatologic assessment including autoimmune serology, musculoskeletal sonography, and electromyography (EMG) in these patients. PATIENTS AND METHODS Postmenopausal patients with stage I to III breast cancer who were taking adjuvant AIs were enrolled (n = 92). Patients who were not receiving hormone treatment were included as a control group (n = 28). Musculoskeletal sonography and EMG were applied to the patients and the controls along with markers of autoimmunity. RESULTS Thirty patients (32.6%) reported to have AI-related new-onset or worsening arthralgia. The most commonly affected joints were knee (70%), wrist (70%), and small joints of the hand (63%). Patients taking AIs had increased tendon thicknesses compared with those who never received AIs (P < .001). Patients with AI-related arthralgia had higher rates of effusion in hand joints/tendons than those without arthralgia (P = .033). More patients with AI-related arthralgia had EMG findings consistent with carpal tunnel syndrome (CTS) than those without arthralgia (P = .024). No significant difference was observed in erythrocyte sedimentation rates, C-reactive protein, antinuclear antibody, antidouble stranded DNA antibody, rheumatoid factor, or anticyclic citrullinated peptide levels between patients and controls or between those with and without arthralgia. CONCLUSION Patients with AI-related arthralgia often show tenosynovial changes suggesting tenosynovitis, exerting local problems but lacking a systemic inflammatory component. Our finding of increased CTS frequency also supports this hypothesis.

Cytogenetic findings‐in 19 malignant bone tumors

Background. The majority of karyotypes observed in osteosarcomas (OS) and chondrosarcomas (CS) are complex, Specific chromosomal abnormalities have not yet been characterized in either tumor except for a ring chromosome in parosteal OS. The purpose of this study was to determine recurrent chromosomal abnormalities and establish a possible correlation between the cytogenetic changes and the pathologic findings.

Breast cancer subtypes and outcomes of central nervous system metastases

Central nervous system (CNS) metastases are detected in up to one third of patients with advanced breast cancer, but their incidence and outcomes by breast cancer subtypes are not precisely documented. Herein, we retrospectively analyzed clinicopathologic data of 259 breast cancer patients with CNS metastases to evaluate the association between breast cancer subtypes and CNS metastasis. The patient groups were classified according to their hormone receptor status and HER-2 expression. Median follow-up time among the patients was 42 months and median survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing group, median time period between the diagnosis of breast cancer and the detection of CNS metastasis (15.9 months) was significantly shorter compared to the other groups (p = 0.01). The triple negative group had the shortest median survival time after CNS metastasis (6.6 months), although statistically not significant (p = 0.3). In multivariate Cox regression analyses, having solitary CNS metastasis (HR 0.4, 95% CI; 0.2-0.7, p = 0.004), and receiving chemotherapy after CNS metastasis (HR 0.4, 95% CI; 0.287-0.772, p = 0.003) were independent prognostic factors for increasing survival after CNS metastasis. In conclusion, new and effective treatment strategies are required for breast carcinoma patients with brain metastasis considering the positive effect of the treatment on survival.

Primary Breast Lymphomas: A Retrospective Analysis of Twelve Cases

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkins lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Chromosome 7 biclonality in uterine leiomyoma

Biclonal chromosome complements in uterine leiomyoma have been reported occasionally. These previous studies reported the presence of two unrelated clones containing mainly t(12;14) and del(7). We describe four cases of typical leiomyoma displaying two clones, both involving chromosome 7 but with a different deletion in each of the two clones. For two of the tumors, the biclonal origin is the only possible explanation; for the remaining two cases, the origin of the two deleted chromosomes 7 could also be explained by clonal evolution, since the more proximal deletion on chromosome 7 in one clone appears to be subsequent to the deletion of the other clone. Even in these cases, however, the biclonal origin cannot be excluded completely. Despite the mechanism of origin, deletion of chromosome 7 is the most common cytogenetic abnormality in leiomyoma, indicating that loss of genetic material from the long arm of this chromosome is critical for tumor development.

Stem cell-related markers in primary breast cancers and associated metastatic lesions.

It has been reported previously that: (1) normal-breast epithelial cells that are CD24−/44+ express higher levels of stem/progenitor cell-associated genes; (2) cancer cells that have undergone epithelial to mesenchymal transition display CD24−/44+ cell-surface expression, a marker for breast cancer stem cells; (3) loss of E-cadherin is a preliminary step in epithelial to mesenchymal transition; and (4) vimentin is a marker of mesenchymal phenotype. We hypothesized that stem cell subpopulations would be more frequent in metastatic than in primary tumors. Therefore we assessed by immunohistochemical analysis, tissue microarrays containing tissue from primary and associated metastatic breast cancers for expression of CD24, CD44, E-cadherin and vimentin to evaluate candidate cancer-initiating cell populations in breast cancer subtypes and metastatic lesions. The occurrence of CD24−/44+ and CD24+/44− cells did not differ in primary vs matched lymph node or distant and locoregional metastatic lesions; E-cadherin expression was decreased in primary vs lymph node metastases (P=0.018) but not decreased in distant and locoregional metastases relative to primary tumor, whereas vimentin, was more frequently expressed in lymph node and distant and locoregional metastases (P=0.013, P=0.004) than in matched primary cancers. Thus, the frequency of CD24−/44+ cells does not differ in metastases relative to the primary breast cancer but differs by tumor stage and subtype.

Involvement of 10q22 in leiomyoma

Cytogenetic investigation of uterine leiomyomas revealed a rearranged 10q22 present in nine tumors as a clonal change in most of the cells analyzed. These findings indicate that abnormalities involving chromosome 10 and, particularly 10q22, may characterize a cytogenetic subgroup of uterine leiomyomas.

Metastasis to the breast from nonmammarian solid neoplasms: a report of five cases.

Primary breast carcinoma is the commonest neoplasm in women. Although rare, metastases of solid tumors from elsewhere to the breast may occur. Apart from cross-lymphatic metastasis from contralateral primary breast carcinoma, hematopoietic neoplasms occasionally involve the breast. As far as we know, less than 500 patients with secondary extramammary solid neoplasms involving the breasts have been reported in the English literature, of which malignant melanoma and lung tumors constitute the leading cause. Herein, five additional adult cases are reported and literature is reviewed. Two of the patients had primary rhabdomyosarcomas, two ovarian carcinomas, and one colon carcinoma. In one case with ovarian carcinoma, breast mass was the only manifestations of the disease relapse. All, except one with disseminated disease, had pathological diagnosis. Two of the patients died soon after the detection of breast metastasis. As a result, breast mass can be the first manifestation of relapse or part of a disseminated disease, and usually predicts poor survival.

Deletion 1p in a Low-Grade Chondrosarcoma in a Patient with Ollier Disease

Ollier disease is an uncommon, nonhereditary developmental disorder affecting enchondral ossification. Cytogenetic analysis of low-grade chondrosarcoma in a patient with Ollier disease (multiple enchondromatosis) revealed an interstitial deletion, del(1)(p11p31.2), as the only chromosome abnormality. This is the first cytogenetic study of a chondrosarcoma in a patient with Ollier disease. Such patients are at risk of developing chondrosarcoma and, because del(1p) is frequent in chondrosarcoma, it is suggested that this cytogenetic finding is associated with early chondrosarcomatous transformation.