Ekrem Yavuz

HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: a proof of principle study.

DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age‐matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3‐fold by high HOXA9 methylation for all stages, and 14.8‐fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention.

Multimodality imaging features of idiopathic granulomatous mastitis: outcome of 12 years of experience.

PurposeThis study was done to determine mammographic, sonographic and magnetic resonance imaging (MRI) appearances of idiopathic granulomatous mastitis, an entity clinically and radiographically resembling breast carcinoma.Materials and methodsA total of 36 women (mean age 37 years, range 21–51 years) with histopathological diagnosis of idiopathic granulomatous mastitis were enrolled in the study. The Breast Imaging Reporting and Data System (BI-RADS) was used to categorise the levels of suspicion of malignancy on mammography. Mammography findings were classified also according to density, margin, architectural distortion and number of lesions. Lesions were classified according to number, heterogeneity and echogenic features on sonography. Dynamic MRI findings were categorised as enhancing mass lesion, nonmass lesion or both mass lesions and nonmass lesions together. Subclassification criteria for MRI included lesion shape, margin, border and internal enhancement pattern.ResultsThe most common mammographic finding was either focal or diffuse asymmetric density (n=15, 44%). The most common sonographic findings were solitary or multiple circumscribed heterogeneous hypoechoic masses (n=19, 52%). Among other sonographic findings were diffuse abscess formation with fistulae and massive parenchymal heterogeneity and hypoechogenicity in 12 (33%) and five (13%) women, respectively. On MRI, enhancing mass lesions were detected in 24 patients, whereas enhancing nonmass lesions were observed in 28. Sixteen patients had both enhancing mass lesions and nonmass lesions together.ConclusionsAlthough not characteristic for this entity, asymmetric density on mammography, solitary or multiple clustered heterogeneous hypoechogenicity with a tubular configuration on sonography and round, smooth-contoured masslike lesion with rim enhancement or segmental non-mass-like lesion on MRI are the most common features of the disease.RiassuntoObiettivoLo scopo del lavoro è determinare gli aspetti in mammografia, ecografia e risonanza magnetica della mastite granulomatosa idiopatica, un’entità clinicamente e radiologicamente simile al carcinoma mammario.Materiali e metodiSono state arruolate nello studio 36 donne (età media: 37 anni, range: 21–51 anni) con diagnosi isto-patologica di mastite granulomatosa idiopatica. è stato utilizzato il Breast Imaging Reporting and Data System (BI-RADS) per classificare il livello di sospetto e di malignità sulla base della mammografia. I rilievi mammografici sono stati classificati anche in base a densità, margini, distorsione strutturale e numero di lesioni. Le lesioni sono state classificate all’ecografia secondo il numero, l’eterogeneità e le caratteristiche di ecogenicità. I reperti sono stati classificati in risonanza magnetica come lesioni con aumentato enhancement di tipo masslike, non-masslike, o contestualmente masslike e non-masslike. Ulteriori criteri in risonanza magnetica hanno incluso forma, margini, bordi e pattern interno di enhancement della lesione.RisultatiIl rilievo mammografico più comune era caratterizzato da densità asimmetriche sia focali che diffuse (n=15, 44%). I reperti ecografici più comuni erano masse circoscritte, solitarie o multiple, eterogenee ed ipoecogene (n=19, 52%). Altri segni ecografici tipici erano diffuse formazioni ascessuali con fistole, caratterizzate da intensa eterogeneità in 12 (33%) donne ed ipoecogenicità parenchimale in 5 (13%) donne. Sulla base della risonanza magnetica, lesioni masslike sono state rilevate in 24 pazienti, mentre lesioni non-masslike sono state osservate in 28 donne. Sedici pazienti avevano contemporaneamente lesioni masslike e non-masslike.ConclusioniSebbene non specifiche di questa entità, le più comuni caratteristiche della mastite granulomatosa idiopatica sono risultate essere: lesioni con densità asimmetrica alla mammografia, lesioni eterogeneamente ipoecogne, solitarie o multiple, con configurazione tubulare, in ecografia, e lesioni masslike, rotondeggianti a margini lisci, con enhancement anulare, o lesioni segmentate non-masslike, in risonanza magnetica.

Comparison of different injection sites of radionuclide for sentinel lymph node detection in breast cancer: single institution experience.

Background: There are still ongoing controversies about several aspects of lymphatic mapping and sentinel lymph node biopsy for breast cancer, including injection site of radioisotope and blue dye. This study aims to evaluate the success rate of different radiocolloid injection techniques in the detection of sentinel lymph nodes (SLN) in early breast cancer. Study Design: One hundred ninety-two women with early breast cancer were included. For SLN mapping with lymphoscintigraphy (LSG), 5 different injections were used. Group A (36 patients) had 4 peritumoral (PT), group B (n = 36) had 1 subdermal (SD) injection of Tc-99m rhenium sulfide colloid over the tumor quadrant. Group C (59 patients) had 1 PT and 1 SD combined injections. In group D (56 patients), lymphatic mapping was performed with 2 intradermal periareolar (ID-PA) injections. In group E (n = 41), 2 ID-PA and 1 PT combined injections were performed. Early dynamic and delayed images were obtained. A surgical gamma probe was used to explore the SLNs. Surgical specimens were evaluated histopathologically. The SLN identification rate, false negative rate, and comparison of groups were evaluated by statistical methods. Results: The SLN identification rate by LSG in groups A, B, C, D, and E were 72%; 92%, 93.2%, 98%, and 95%, respectively. The highest detection rates for the axilla (98%) and mammary internal (MI) drainage (22%) were obtained with ID-PA injections and a peritumoral injection, respectively. Seventy of 192 patients (36.4%) had positive axillary lymph nodes. The only statistically significant difference was between the PT and SD injection groups in axillary SLN identification rate by LSG (P = 0.016). Conclusion: The success rate was superior with intradermal periareolar injection compared with PT and SD injection to visualize the axillary SLN. However, PT deep injection combined with ID-PA injections may be more favorable to demonstrate the primary internal mammary (IM) lymphatic drainage.

Diagnostic value of PET/CT is similar to that of conventional MRI and even better for detecting small peritoneal implants in patients with recurrent ovarian cancer.

ObjectiveThe aim of this study was to evaluate the diagnostic value of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT in comparison with MRI for the detection of recurrent ovarian cancer. MethodsForty-seven patients with suspected ovarian cancer recurrence after total ablative or cytoreductive surgery, as well as neoadjuvant or adjuvant chemotherapy, who had undergone 18F-FDG PET/CT imaging were recruited for the present study. All patients also underwent MRI within a month of 18F-FDG PET/CT for the same purpose. Recurrent cancer in the abdomen and pelvis was evaluated in each of the 47 patients and classified as either distant metastasis or local pelvic recurrence involving the vaginal stump, peritoneal implants, supradiaphragmatic region, and/or abdominal and pelvic lymph nodes. Special attention was paid to peritoneal implants. These were divided into five groups according to size of the implants: less than 0.5 cm (group 1), 0.5–1 cm (group 2), 1–2 cm (group 3), 2–3 cm (group 4), and larger than 3 cm (group 5). PET/CT findings were compared with abdominopelvic MR findings. Statistical analysis was carried out using the Wilcoxon signed rank test. ResultsThirty-nine of 47 patients were found to have recurrent ovarian cancer. Both PET/CT and MRI were negative for recurrence in six patients. Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT were 97.5, 100, 100, 87.5, and 97.8%, respectively, whereas those of MRI were 95, 85.7, 97.4, 75, and 93.6%, respectively. For the peritoneal implants in groups 2 and 3, the sensitivity, negative predictive value, and diagnostic accuracy values of PET/CT were significantly better than those of MRI (P<0.05). ConclusionThe present study revealed that PET/CT is similar to conventional MRI for the detection of recurrent ovarian cancer. PET/CT has greater accuracy in the detection of small-to-medium-sized (<2 cm) peritoneal implants compared with MRI. This may affect surgical decision making.

Comparison of subdermal and peritumoral injection techniques of lymphoscintigraphy to determine the sentinel lymph node in breast cancer

Purpose: The purpose of this study was to evaluate 2 different injection techniques for lymphoscintigraphy to determine the axillary sentinel lymph node (SLN) in patients with breast cancer. Methods: Thirty-six patients with early breast cancer were studied prospectively. Both peritumoral (PT) and subdermal (SD) injections were performed on each patient with Tc-99m rhenium sulfide colloid. PT injections were done 1 to 8 days before surgery and SD injections were done on the day of operation. An intraoperative gamma probe was used to explore the axillary SLNs prior to tumor excision and axillary dissection. All surgical specimens were evaluated histopathologically. Results: In 19 of 36 patients, the same lymphatic drainage sites were observed with both techniques. Of these, 17 patients showed only axillary, 1 showed axillary and internal mammary (IM), and 1 showed axillary and subclavicular drainage sites. With PT injections 26 of 36 patients (72%), and with SD injections 33 of 36 patients (92%), showed axillary drainage and axillary SLNs. With PT injections 9 patients, and with SD injections only 2 patients, did not show any drainage site. During the operation with a gamma probe, axillary SLNs were excised in 35 patients (success rate, 97%). IM drainage was seen in 8 of 36 patients who underwent PT injections and in 3 of 36 with SD injections. Conclusion: The success rate was found to be higher with the SD injection technique than with PT injections to visualize the axillary SLN. To increase the visualization of both axillary and IM SLNs, it may be useful to perform lymphoscintigraphy with SD and PT injections together.

Cyclic sciatica caused by infiltrative endometriosis: MRI findings

Endometriosis, an important gynecological disorder of reproductive women, affects most commonly the ovaries and less frequently the gastrointestinal tract, chest, urinary tract, and soft tissues. Endometriosis classically appears on MRI as a mass with a large cystic component and variable signal intensities on T1- and T2-weighted images due to the presence of variable degradation of hemorrhagic products. Endometriosis in an atypical location, an infiltrative appearance and without cystic-hemorrhagic components has rarely been described. We report on a 33-year-old woman with cyclic sciatica due to histologically documented infiltrative endometriosis involving the area of the left sciatic notch.

Angiogenesis and p53 protein expression in breast cancer: prognostic roles and interrelationships.

The authors have analyzed, on the one hand, the prognostic impact of microvessel density (MVD) and p53 protein expression in patients with breast cancer, and on the other hand, the correlation between the microvascular pattern and the p53 protein expression. Tumors from 120 patients whose paraffin-embedded tissue blocks were available were analyzed using the immunohistochemical method. MVD and p53 protein expression were correlated with histologic grade and tumor size, respectively. The patients with highly vascularized tumor (high MVD) had decreased overall survival (p = 0.04), whereas overexpressed p53 patients did not. In multivariate analysis, axillary lymph node status (p = 0.007), tumor size (p = 0.01), and MVD (p = 0.02) showed important prognostic influence on overall survival. When the simultaneous influence of MVD and p53 protein expression on survival were analyzed, no interrelationship was detected. The results demonstrate the prognostic impact of MVD on overall survival in breast cancer and no association between MVD and p53 protein expression.

An ultrasensitive tumor enriched flow-cytometric assay for detection of isolated tumor cells in bone marrow of patients with breast cancer

BACKGROUND An ultrasensitive tumor enriched flow-cytometric assay was used to determine its feasibility in detection of isolated tumor cells (ITC) in bone marrow (BM) of patients with breast cancer. METHODS Epithelial cells were removed by magnetic microbeads conjugated with an anti-cytokeratin 7/8 monoclonal antibody to enrich tumor cells in BM samples. A specific gate for MCF-7 breast cancer cells (gate(MCF-7 cells)) was also taken into consideration in addition to a gate including all enriched BM cells (gate(enriched BM cells)) in flow-cytometric analysis to enhance the specificity of the method. RESULTS Nineteen patients with stage I/II were evaluated. Ten patients (53%) were found to have cytokeratin positive (CK(+)) cells according to the gate(enriched BM cells) whereas 6 patients (32%) had CK(+) cells when the gate(MCF-7 cells) was taken into account. CONCLUSIONS New strategies in nonmorphological ultrasensitive techniques might be useful to categorize patients with ITCs having different tumor morphology and characteristics.

Positive or close margins in breast conserving surgery: Is re-excision always necessary?

BACKGROUND More than half of re-excision specimens after breast conserving surgery (BCS) are found to be free of residual tumor at definitive histology. The aim of this study was to identify clinicopathological factors along with intrinsic subtypes of the tumor (luminal A, luminal B, HER2-overexpressing, triple-negative) associated with residual tumor in re-excision or mastectomy specimen. METHODS Two hundred forty-eight patients with initial BCS, who underwent one or more re-excisions or mastectomy because of close or positive margins were reviewed. RESULTS Residual cancer was found in 50% of re-excision(s) or mastectomy specimens. Patients with multifocality (vs unifocality; OR = 5.2; 95% CI, 2.6-10.4) or positive nodes (vs negative nodes; OR = 2.5; 95% CI, 1.4-4.4), or positive margins (vs close margins; OR = 1.7; 95% CI = 1.0-2.9) were more likely to have residual tumor in re-excision or mastectomy specimen compared to others. CONCLUSION Our results suggest that further surgery is often indicated in patients with node positive or multifocal cancers or positive margins after BCS since residual disease cannot be ruled out. Re-excision or mastectomy could be omitted in patients with close margins with favorable factors such unifocal tumor or node negative disease.

The values of intratumoral mast cell count and Ki-67 immunoreactivity index in differential diagnosis of uterine smooth muscle neoplasms

In this study, the role of the count of intratumoral mast cells was examined and compared with the proliferative activity exhibited by Ki‐67 indices in the differential diagnosis of uterine smooth muscle tumors. Sixteen cases of leiomyosarcoma, nine cases of atypical leiomyoma and 16 cases of ordinary leiomyoma were included. The pathological features of the cases were determined by reviewing the archive materials including the patient records and hematoxylin‐eosin‐stained sections. Toluidine blue stain was used to highlight the intratumoral mast cells and they were counted in at least 40 high power fields. A standard streptavidin–biotin method was applied to the sections to highlight the Ki‐67 immunoreactive tumor cell nuclei. These proliferative cells were counted in at least 10 high‐power fields. Atypical leiomyomas tended to have a higher quantity of intratumoral mast cells than leiomyosarcomas and ordinary leiomyomas (P= 0.027 and P= 0.021, respectively). Leiomyosarcomas tended to have higher Ki‐67 immunoreactivity rates than atypical leiomyomas, although the difference was not statistically significant (P= 0.82). We concluded that the quantity of intratumoral mast cells is useful in the differential diagnosis between leiomyosarcomas and atypical leiomyomas, while the cell proliferation rate expressed by Ki‐67 immunoreactivity has a limited value.