Altered Expression of RB and pRB in Tissue Arrays of Primary Breast Cancers and Matched Axillary Lymph Node Metastases.

Objectives: The retinoblastoma (RB) pathway is crucial in the development and progression of many cancers. To better understand the biology of progressive breast cancer (BC), we examined protein expression of the RB pathway in primary BCs and matched axillary lymph node metastases (LM). Methods: Immunohistochemistry was used to evaluate cyclin D1, CDK4/6, RB, phosphorylated RB (pRB), and E2F1 expression in tissue arrays containing cores of 50 primary BCs and matched LM. The number of positive tumor cells and staining intensity were scored. Results: The proteins were localized in the nucleus, while CDK6 was detected in the cytoplasm and CDK4 was found in both. pRB and E2F1 showed higher expression in matched LM than in primary tumors. Expression of these proteins differed significantly by the percentage of positive tumor cells, while proteins in the proximal portion of the RB pathway showed no significant differences. The main path of alteration consisted of high pRB in primary BC, remaining pRB high in the majority of LM, variations occurring in fewer cases. All matched LM of the few primary tumors that had unaltered RB and pRB expression showed changes in RB or pRB expression. Conclusion: Expression of pRB and E2F1 was significantly higher in LM than in primary BC. A majority of cancers with LM showed altered RB or pRB expression, suggesting that proteins downstream in the RB pathway play a critical role in metastatic BC and disease progression. So looking at the RB pathway could be an option for chemotherapy decisions in patients with only few LM.

Epithelial and tumor-associated endothelial expression of B7-H3 in cervical carcinoma: relation with CD8+ intraepithelial lymphocytes, FIGO stage, and phosphohistone H3 (PHH3) reactivity.

B7-H3 is a transmembrane protein and a member of the B7 family of immune regulatory ligands. It exerts both inhibitory and stimulatory effects on the activation of T cells. We investigated the expression of B7-H3 in invasive squamous cell carcinoma (ISCC) of the uterine cervix by immunohistochemistry, and aimed to determine whether expression of this factor is involved in the progression of the morphologic spectrum from normal cervical epithelia to cervical intraepithelial neoplasia and cervical ISCC. In addition, we sought to examine the relation of B7-H3 to the abundance of tumor-infiltrating and tumor-associated CD8(+) lymphocytes and to the evidence of phosphohistone H3, which is a core histone protein detected during mitosis. B7-H3 immunostaining was scored with regard to quantity and intensity of positively stained cells, and was noted in membranous and cytoplasmic patterns in epithelial cells and on endothelia of stromal blood vessels. Compared with those in intraepithelial neoplasias, immunoscores were significantly increased in ISCC (P<0.0001 for epithelial and endothelial expression, respectively). High scoring was associated with International Federation of Gynecology and Obstetrics stages IB and higher. Immunoscores of epithelial and endothelial B7-H3 expression were correlated significantly (P=0.0358). Epithelial and endothelial expression of B7-H3 was inversely related with CD8(+) tumor-infiltrating lymphocyte (P<0.0001). Moderate/strong B7-H3 epithelial as well as endothelial expression was mutually increased with intermediate/strong phosphohistone H3 scores (P=0.0396 and P=0.0483, respectively). There was no statistical relation with survival; however, no patient with negative scoring died of her tumor. Our results indicate that B7-H3 expression in cervical ISCC may play an important role in overcoming CD8(+) T-cell immunoregulation to acquire aggressive growth.

Role of endotracheal stenting in tracheal reconstruction surgery-retrospective analysis.

OBJECTIVE: To review a single institution experience with tracheal stenosis treatment and to define a role of endotracheal stenting in tracheal reconstruction surgery. PATIENTS AND METHODS: In the period between January 1991 and January 2003, 163 patients underwent tracheal reconstruction. There were 114 males and 49 females in age range from 0.5 to 79 years (mean 43.2 years). Indications for reconstruction were: posttracheostomic (PostTS) and postintubation (PostINT) stenoses in 111 cases, tumor-stenosis in 24 cases, tracheo-esophageal fistulas (T-Efist) in 17 cases, traumatic laesions in six and functional stenosis in five cases. For these indications, the following procedures were performed: segmental tracheal resection in 87 cases, stenting in 68 cases (by our own modification of Montgomery T-tube in 65 cases and by other traditional endo-stents in three cases). Primary suture of traumatic tracheal wall was performed in five cases. Three cases involved laser intervention and tumor resections, respectively. RESULTS: Segmental tracheal resection (n = 87) was successful in almost all the cases (96%). T-tube was applied in 65 cases; the indications included: PostTS and PostINT stenoses in 38 cases, tumors in 17 cases, T-E fistulas in seven cases and functional stenosis in three cases. Twenty-seven patients (41.6%) were successfully treated by this modality. In 19 patients (29.2%), the stenting is still continuing, but they are candidates for extraction of the T-tube in near future. In 19 patients (29.2%) with malignant stenoses, the T-tube was applied only as a palliation. All these patients died due to their underlying malignant disease; the follow-up ranged from 2 to 18 months. CONCLUSION: Tracheal stenosis is a serious, life-threatening disease with increasing incidence. In our study, the best results were achieved by segmental tracheal resection. However, the endotracheal stenting is the method of choice, when the segmental resection cannot be performed. The management of tracheal stenosis reconstruction by our own modification of Montgomery T-tube is being presented.