Merih Guray

Estrogen/progesterone receptor negativity and HER2 positivity predict locoregional recurrence in patients with T1a,bN0 breast cancer

PURPOSE Data have suggested that the molecular features of breast cancer are important determinants of outcome; however, few studies have correlated these features with locoregional recurrence (LRR). In the present study, we evaluated estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as predictors of LRR in patients with lymph node-negative disease and tumors < or = 1cm, because these patients often do not receive adjuvant chemotherapy or trastuzumab. METHODS AND MATERIALS The data from 911 patients with stage T1a,bN0 breast cancer who had received definitive treatment at our institution between 1997 and 2002 were retrospectively reviewed. We prospectively analyzed ER/PR/HER2 expression from the archival tissue blocks of 756 patients. These 756 patients represented the cohort for the present study. RESULTS With a median follow-up of 6.0 years, the 5- and 8-year Kaplan-Meier LRR rate was 1.6% and 5.9%, respectively, with no difference noted in those who underwent breast conservation therapy vs. mastectomy (p=.347). The 8-year LRR rates were greater in the patients with ER-negative (10.6% vs. 4.2%, p=.016), PR-negative (9.0% vs. 4.2%, p=.009), or HER2-positive (17.5% vs. 3.9%, p=0.009) tumors. On multivariate analysis, ER-negative and PR-negative disease (hazard ratio, 2.37; p=.046) and HER2-positive disease (hazard ratio, 3.13, p=.016) independently predicted for LRR. CONCLUSION Patients with ER/PR-negative or HER2-positive T1a,bN0 breast cancer had a greater risk of LRR. Therapeutic strategies, such as the use of chemotherapy and/or anti-HER2 therapies, should be considered for future clinical trials for these patients.

Expression of p53 and mdm2 and Their Significance in Recurrence of Superficial Bladder Cancer

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder

OBJECTIVES To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Prognostic significance of occult axillary lymph node metastases after chemotherapy-induced pathologic complete response of cytologically proven axillary lymph node metastases from breast cancer

Primary systemic chemotherapy has been a standard of care for the management of locally advanced breast cancer (LABC) patients and has increasingly been used for patients with large operable breast cancer. Pathologic complete response (pCR) of axillary lymph node metastases predicted an excellent probability of long‐term disease‐free and overall survival. Although the clinical significance of occult lymph node metastases in patients with breast cancer was extensively studied, their prognostic value in patients with LABC after primary chemotherapy was not known. This study evaluated the detection rate and clinical significance of occult lymph node metastases in lymph nodes that contained metastatic carcinoma at the time of initial diagnosis and converted to negative based on routine pathologic examination after primary systemic chemotherapy.

Expression of Bcl-2, Bax and p53 proteins in pituitary adenomas an immunohistochemical study

Aims and Background Although pituitary adenomas are usually benign lesions, their growth rate is highly variable and unpredictable. Apoptosis appears to be an important process in neoplastic lesions. The purpose of this study was to investigate the expression of apoptosis-related proteins including Bcl-2, bax and p53 in pituitary adenomas and its correlation with hormone function, tumor size, local control, and proliferative activity. Study Design The expression of Bcl-2, Bax and p53 proteins and hormonal function were determined in formalin-fixed, paraffin-embedded tissue from 41 untreated pituitary adenomas using immunohistochemistry. The patients were followed for a median of 60 months (range, 12 to 95). Patient charts were reviewed to record tumor recurrence and size. Tumor proliferative activity was assessed by immunohistochemistry using Ki-67 antibody. Results Of 41 pituitary adenomas, 26 (63%) were hormone-secreting and 15 (37%) non-functioning, 34 (83%) were macroadenoma and 7 (17%) microadenoma, and 15 (37%) showed local relapse. Six (14%) adenomas were of low proliferative activity, whereas the others (86%) were non-proliferative. Immunohistochemically, 31 adenomas (75%) showed bcl-2 positivity, 37 (90%) bax positivity, and 7 (17%) p53 positivity. Statistical analysis revealed that Bcl-2 protein expression significantly diminished in prolactin-secreting and non-functioning adenomas (P = 0.005 and P = 0.006, respectively), and increased in growth hormone-secreting adenomas (P = 0.003). In addition, expression of bax protein significantly decreased in recurrent tumors, in contrast to p53 protein, which showed a significant increase (P = 0.03 and P = 0.002, respectively). Conclusions We think that apoptosis-related proteins such as Bcl-2, Bax and p53 may be significantly related to hormone function and local control in pituitary adenomas.

Papillary carcinoma arising in subhyoid ectopic thyroid gland with no orthotopic thyroid tissue

Ectopic thyroid gland with no orthotopic thyroid tissue is extremely rare. The authors present a case of a follicular variant of papillary carcinoma developed from an ectopic thyroid gland with no orthotopic thyroid tissue.

Breast myxoma: Radiologic and histopathologic features.

Abstract:  Myxomas are benign mesenchymal tumors, which rarely develop in the breast. Histologically, stellate, round, and spindle‐shaped cells with vesicular nuclei and scant cytoplasm are scattered in the myxoid stroma. We present a case of this rare type of breast tumor with sonographic and mammographic findings.

Patients With Only 1 Positive Hormone Receptor Have Increased Locoregional Recurrence Compared With Patients With Estrogen Receptor-Positive Progesterone Receptor-Positive Disease in Very Early Stage Breast Cancer*

Estrogen receptor (ER) and progesterone receptor (PR) are important prognostic and predictive biomarkers in breast cancer. Patients with tumors positive for either receptor are generally considered hormone receptor‐positive for treatment decisions. However, some data suggest that patients with ER+/PR− or ER−/PR+ tumors may have worse outcomes than those with ER+/PR+ tumors. Few data correlate these biomarkers with locoregional (LR) recurrence.

Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas.

Objective: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity. Methods: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki–67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1–3 and the Ki–67–labelling index was determined as a percentage of positively staining tumor cells. Results: An inverse relationship was found between pS2 expression and Ki–67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki–67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively). Conclusion: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.

In Situ Hybridization Analysis of Invasive Breast Carcinomas with Immunohistochemically Negative Her-2 Status (A National Multicenter Study)

Abstract Objective: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). Material and Method: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. Results: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. Conclusion: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice. ÖZ Amaç: Bu calışmada, Her-2 durumları onceden immunohistokimyasal olarak skor 0 veya 1+ olarak tanımlanmış meme karsinomu olgularında silver in situ hibridizasyon ile tekrar test yapılarak Her-2 pozitiflik oranının tespit edilmesi amaclanmıştır. Gereç ve Yöntem: Calışmada 9 merkezin katkısıyla, 552 olgu değerlendirildi. Calışmaya, Her-2 immunohistokimya sonucu 0/1+ bulunmuş meme kanseri olguları alındı. Bu olgulara ait parafin blok kesitlerinde merkez laboratuvarında Her-2 durumu silver in situ hibridizasyon yontemiyle yeniden değerlendirildi. Her-2 gen amplifikasyonu, Her-2/ CEP 17 oranının 2,2’den fazla olması şeklinde tanımlandı. Her-2/CEP 17 oranı 1,8-2,0 arasındaki olgular şupheli ve 1,8’in altındaki olgular ise negatif olarak değerlendirildi. Bulgular: 552 olgunun in situ hibridizasyon ile tekrar değerlendirmesinde skor 0 olan olguların 11’i (%3,2) ve skor 1+ olanların 11’i (%5,3) olmak uzere toplam 22 olguda Her-2 gen amplifikasyonu saptandı. Skor 0 ve 1+ olan olgulardaki Her-2 gen amplifikasyon saptama oranları calışma merkezlerinde %0 ile %10,48 arasında değişmekteydi. Skor 0 olan olguların 28’inde (%8,1) ve skor 1+ olan olguların 25’inde (%12,1) polizomi goruldu. Polizomi olan olgulardan 5’inde (%9,4) Her-2 gen amplifikasyonu olduğu, 48’inde ise (%90,6) olmadığı belirlendi. Sonuç: Calışmanın bulguları, anti- Her-2 tedaviden yararlanma potansiyeli olan bir populasyonun (%3,98) immunohistokimya yontemi ile gozden kacabileceğini gostermektedir. Bu sonuc, ozellikle de cok sayıda meme kanseri olgusuyla karşılaşılan merkezi laboratuvarlarda kalite guvencesinin onemini ortaya koymaktadır.