Sema Bircan

Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ER-alpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.

Immunohistochemical galectin-3 expression in non-melanoma skin cancers

Galectin-3 is a ss-galactoside-binding lectin. It participates in a variety of normal and pathologic processes, including cancer progression. In this study, we evaluated the pattern of expression of galectin-3 in cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and its correlation with the grade of differentiation in SCC and tumor size. Galectin-3 expression was evaluated by immunohistochemistry in 31 SCCs, 30 BCCs, and 29 non-tumoral skin samples. Galectin-3 expression was higher in normal epidermis than in non-melanoma skin cancers, except for cytoplasmic immunoreactivity in SCC. Cytoplasmic galectin-3 immunoreactivity was significantly higher than nuclear immunoreactivity in non-melanoma skin cancers. Cytoplasmic galectin-3 immunoreactivity was significantly higher in SCC than in both circumscribed and infiltrative BCCs, but no difference was detected between these two types of BCC. Cytoplasmic galectin-3 immunoreactivity predominated within SCCs (p=0.000), and a positive correlation was detected between tumor size and cytoplasmic immunoreactivity (r=0.385, p=0.043). There was no correlation between galectin-3 staining and tumor differentiation and lymph node metastasis. Decreased nuclear galectin-3 expression and cytoplasmic immunoreactivity in tumors are important factors in the progression from the normal to the cancerous state in non-melanoma skin cancers. We speculate that cytoplasmic galectin-3 expression may be one of the factors that contribute to tumor aggressiveness in SCC.

The expression of p63 in basal cell carcinomas and association with histological differentiation

Background:  We aim to examine p63 expression in basal cell carcinomas (BCCs) and to investigate association with their histopathological differentiation subtypes.

Maspin, VEGF and p53 Expression in Small Biopsies of Primary Advanced Lung Cancer and Relationship with Clinicopathologic Parameters

Maspin, one of the serine protease inhibitors, has been shown to inhibit tumor progression and metastasis. We aimed to investigate maspin, p53 and VEGF expression in patients with squamous cell carcinoma (SCC), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). The study included 28 SCC, 18AC, 17 SCLC biopsy samples. We used the streptavidin biotin immunoperoxidase method to test for maspin, p53 and VEGF antibodies. Medical records of these patients were reviewed from archival files. Cytoplasmic maspin expression was detected in 89.3%, 77.8%, 52.9% of SCC, AC and SCLC, respectively. The rate was significantly higher in non-small cell lung cancer (NSCLC) and SCC than SCLC (p = 0.013, p = 0.021, respectively). The mean percentages of maspin expression were significantly higher in NSCLC, SCC and AC than in SCLC (p = 0.0001, p = 0.0001, p = 0.038, respectively). In ACs, maspin and p53 expressions were correlated, although this was not statistically significant (p = 0.053, r = 0.464), and maspin positive cases had a significantly higher T status compared to negative cases (p = 0.036). In SCC, the stage of disease was positively correlated with p53 (p = 0.007, r = 0.536) and negatively correlated with VEGF expression (p = 0.013, r = −0.498). Multivariate analysis demonstrated that stage of disease was a significant independent prognostic parameter in NSCLC (95% confidence interval: 1.067–3.969; p = 0.031). Although maspin expression is higher in SCC and AC, and is related with higher T status in AC, our data did not indicate its prognostic significance. Larger scale studies are needed to reveal the exact role of maspin in lung cancer pathogenesis.

The effect of tumor invasion patterns on pathologic stage of bladder urothelial carcinomas.

The aim of this study was to investigate tumor invasion pattern, its heterogeneity and association with histopathological features and stage in invasive urothelial carcinoma of the bladder. We studied 62 cases of invasive urothelial carcinoma of the bladder. World Health Organization (WHO) 1973, WHO/ISUP1998 and WHO 1999 systems were used for tumor grading. Pathologic staging of each case was done according to 1997 TNM system. During evaluation of the slides three main tumor invasion patterns were detected: “nodular”, “trabecular” and “infiltrative”. In addition, homogeneity or heterogeneity of invasion patterns was also recorded for each case. Of sixty-two invasive cases, 17 (27%) had nodular, 36 (58%) trabecular, and 9 (15%) infiltrative invasion pattern. There was a statistically significant difference between invasion patterns in relation to pathologic stage (pT) (p=0.001), but not to grade. Of the 17 cases with nodular invasion pattern and 36 tumors with trabecular invasion pattern, 13 (77%) and 26 (72%) were pT1, respectively, whereas 8 of 9 infiltrative cases (89%) were advanced stage (pT2-3). According to heterogeneity, forty-two cases (68%) had homogeneous, while the remaining 20 (32%) had heterogeneous invasion pattern. Of the 42 homogeneous cases 34 (81%) were pT1, whereas 14 of 20 heterogeneous cases (70%) were advanced stage (p=0.000). The different invasion patterns seem to have a large impact on pathologic stage, especially the infiltrative pattern. In addition, invasion heterogeneity appears to be of value in determination of biologic aggressiveness in urothelial carcinoma.

Beclin 1 and bcl-2 expressions in bladder urothelial tumors and their association with clinicopathological parameters.

Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation, as well as in the development and progression of cancer. The aim of this study was to examine the expression of beclin 1 and bcl-2 in bladder urothelial tumors, and to investigate the relationship between these two markers and clinicopathological parameters. Our study included 84 bladder urothelial tumors and 10 non-tumoral bladder tissues. Immunohistochemistry was performed on tissue microarray (TMA) sections and was evaluated semiquantitatively on the basis of the percentage of positively stained cells (proportion) and staining intensity. A significant association was found between the expression score of beclin 1 and pT stages of the urothelial tumors (p=0.012). Also, the level of beclin 1 expression inversely correlated with histological grade and pT stages (p=0.009, r=-0.284; p=0.001, r=-0.361, respectively). The bcl-2 expression level positively correlated with histological grade and pT stages of the urothelial tumors (p=0.026, r=0.243; p<0.0001, r=0.491, respectively). In addition, the level of beclin 1 expression tended to be inversely correlated with the bcl-2 expression level in urothelial tumors (p=0.055, r=-0.210). According to our data, down-regulation of beclin 1 expression and also bcl-2 overexpression seem to play an important role in the progression and aggressiveness of bladder urothelial tumors.

The relation of beclin 1 and bcl-2 expressions in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue microarray study.

The aim of the present study was to evaluate the expressions of beclin 1 and bcl-2 in prostate cancer (PC) and high grade prostatic intraepithelial neoplasia (HGPIN), and to investigate their relationship with clinicopathological parameters. The study included 30 benign prostatic hyperplasia (BPH), 40 HGPIN and 106 primary PC cases. The expressions of beclin 1 and bcl-2 were assessed semiquantitatively based on both the percentage and intensity of positive staining cells. Beclin 1 was positive in 27 (90%) BPH, 37 (92.5%) HGPIN, and 90 (84.9%) PC cases (p>0.05). Bcl-2 immunostaining was detected in 99 (93.4%) PC, 37 (92.5%) HGPIN, and 9 (30%) BPH cases (p<0.0001). Regarding expression scores, beclin 1 was significantly lower in PC cases than in the HGPIN and BPH groups (p<0.0001), and it was also negatively correlated with Gleason score (p=0.004, r=-0.274). Bcl-2 expression score was significantly higher in PC than in the other groups (p<0.0001), and also positively correlated with Gleason score (p<0.0001, r=0.425). Furthermore, a negative correlation was found between bcl-2 and beclin 1 expression scores in PC cases (p=0.006, r=-0.265). Our results suggest an association between bcl-2 and beclin 1 expressions in malignant transformation of prostate tissue and also in regulating PC cell differentiation, progression and the aggressiveness of PC.

Erythema annulare centrifugum-like mycosis fungoides

A considerable number of recent reports have documented mycosis fungoides resembling many other dermatoses. Due to highly variable presentations and the sometimes non‐specific nature of histological findings, an accurate diagnosis of mycosis fungoides can be difficult. Erythema annulare centrifugum‐like mycosis fungoides with a variety of annular, polycyclic erythematous skin lesions is a recently recognized atypical manifestation of mycosis fungoides, and only a few cases have been reported to date.

Expression of NGF, GDNF and MMP-9 in prostate carcinoma

The aim of the present study was to investigate the immunohistochemical expression of NGF, GDNF and MMP-9 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse their association with the clinicopathological parameters in PC cases. Immunohistochemistry was performed on the tissue microarray (TMA) sections of 30 BPH, 40 HGPIN and 121 primary PC tissues. There was a significant difference regarding the expression of NGF and GDNF between PC and HGPIN (p<0.0001; p<0.0001), and PC and BPH (p=0.001; p<0.0001), but not between HGPIN and BPH (p>0.05). Furthermore MMP-9 expression was significantly different among all groups (PC vs. HGPIN, p<0.0001; PC vs. BPH, p<0.0001; HGPIN vs. BPH, p=0.001). NGF, GDNF and MMP-9 expression was significantly stronger in cases with high Gleason score (p<0.0001, p=0.004, p<0.0001 respectively) and pT stage (p=0.046, p=0.004, p=0.001, respectively) in PC cases. All these markers were also associated with perineural, lymphovascular and extraprostatic invasion (p <0.05). In addition, a positive correlation was found between NGF and MMP-9 (p<0.0001, r=0.435), NGF and GDNF (p<0.0001, r=0.634), and GDNF and MMP-9 (p<0.0001, r=0.670) in PC cases. According to our results we suggest an interaction between NGF, GDNF and MMP-9 during the transition to malignancy in PC. Also this interaction may involve in regulating PC cell differentiation, tumor invasion, progression, and the agressiveness of PC.

Chronic renal failure and macrogenitalia associated with genitourinary neurofibromatosis

Neurofibromatosis (NF) is a genetic disorder of the nervous system that primarily affects the development and growth of neural cell tissues. This disorder is characterized by the development of various tumors, including neurofibromas, neuroniomas, malignant and benign peripheral nerve sheath tumors, and meningiomas. Accompanying skin changes and bone deformities are also common in NF. However, genitourinary involvement in NF is a rare condition, and penile enlargement has been reported only in a few males with plexiform NF. We report a 6-year-old boy with chronic renal failure associated with plexiform neurofibromas of the bladder and prostatic urethra which led to urinary obstruction and macrogenitalia due to genitourinary NF.