Bilateral, buccinator myomucosal advancement flaps to reconstruct central upper labial myomucosal defects after ablation of early-stage cancer in minor salivary glands.

BACKGROUND: Reconstruction of upper labial myomucosal defects is surgically challenging. AIMS: We evaluated whether central defects could be repaired using bilateral, buccinator myomucosal advancement flaps (b-BMAFs). METHODS: We evaluated five patients with early-stage, minor salivary gland mucoepidermoid carcinomas (low-grade [n = 2], intermediate-grade [n = 2], and high-grade [n = 1]) who underwent central, upper labial myomucosal reconstruction using b-BMAFs after cancer ablation. We treated two men and three women aged 25-59 years. Tumors ranged in size from 1.8 × 1.8 to 2.5 × 2.2 cm. Clinical stages were I and II in two and three patients, respectively. Defect dimensions ranged from 2.8 × 2.8 to 3.5 × 3.2 cm. RESULTS: All patients underwent successful reconstruction of central, upper labial myomucosal defects using b-BMAFs and were satisfied with the esthetic results. Adequate orbicularis oris and speech function were maintained. No reduction in mouth opening was observed. Patients were followed up for 24-36 months; one pulmonary metastasis was observed at 36 months postoperatively. CONCLUSION: Placement of b-BMAFs is safe and feasible when reconstructing central, upper labial myomucosal defects after ablation of early-stage, minor salivary gland cancer.

A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma.

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

Analysis of the circular RNA transcriptome in the grade 3 endometrial cancer.

BACKGROUND/AIMS: Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have shown large capabilities in gene regulation. Patients with the grade 3 endometrial cancer (EC) have a generally poor prognosis, and the specific role of circRNAs in the grade 3 EC remains unclear. This study aims to investigate the roles of circRNAs in the grade 3 EC. METHODS: In the current study, we screened the expression profiles of circRNAs taken from two women with the grade 3 EC and adjacent non-cancerous endometrial tissue using circRNAs sequencing. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) of six dysregulated circRNAs was performed to validate the sequencing results. Bioinformatic analyses, including the negative correlation network analyses of circRNAs-microRNAs (miRNAs)-messenger RNAs (mRNAs) and the Cytoscape, were used to delineate the interaction of circRNAs/miRNAs of the entire network. RESULTS: Data of circRNA sequencing showed a significant change in 75,928 unique circRNAs (P<0.05). The upregulated hsa_circ_0039569 and hsa_circ_0001610 and downregulated hsa_circ_0000437, hsa_circ_0001776, and hsa_circ_0009043 were validated by qRT-PCR analysis. Using bioinformatical methods, we found that hsa_circ_0039569 has the MRE of hsa-miR-542-3p and hsa-let-7c-5p. Hsa-miR-542-3p and hsa-let-7c-5p were downregulated in the grade 3 EC validated by qRT-PCR analysis. In the clinicopathological parameters, the expression level of hsa_circ_0039569 was significantly correlated with tumor differentiation (P=0.001). CONCLUSION: This is the first study demonstrated that there were a lot of differences between the tissue of the grade 3 EC and adjacent non-cancerous endometrial in circRNA expression and may offer novel molecular candidates for diagnosis and clinical treatment of the grade 3 EC.

Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma.

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

Bilateral blindness with secondary retinitis pigmentosa following postoperative docetaxel and platinum combination chemotherapy in primary small-cell carcinoma of the endometrium: An unusual case report and review of the literature.

Ocular toxicity is an uncommon complication of cytotoxic chemotherapy. Bilateral blindness with secondary retinitis pigmentosa (RP) following docetaxel and platinum combination chemotherapy at the recommended dose is extremely rare. The present study reports a case of advanced small-cell carcinoma (SCC) of the endometrium in a patient with diabetes mellitus type 2. The patient suffered from RP with a sharp decline in vision after the fourth course of postoperative docetaxel and platinum combination chemotherapy. Unfortunately, the patient developed bilateral blindness after another course of chemotherapy at a reduced dose. No tumor recurrence was observed during the 33 months of follow-up. A total of 35 cases of docetaxel- and/or platinum-induced retinal toxicity were found in the English literature and reviewed. The ischemic and electrophysiological hypotheses may have been implicated in the pathogenesis of ocular toxicity in the present case, particularly with the history of diabetes. Understanding the ocular side effects of this combination chemotherapy may assist gynecological oncologists and ophthalmologists with early recognition and timely intervention before blindness is established.

miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.

Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity.

Management of carotid body tumor and pseudoaneurysm after blunt dissection.

BACKGROUND: Surgical treatment of carotid body tumors remains challenging, and this study evaluated the outcomes of carotid body tumor and pseudoaneurysm after blunt dissection of the tumors. METHODS: Six cases were classified as Shamblin groups I, II, and III (1, 1, and 4 cases, respectively). Tumor size ranged from 2 × 3 to 5 × 6 (median, 3.7 × 4.7) cm. Two patients underwent blunt dissection of the carotid body tumor, two underwent blunt dissection and ligation of the external carotid artery of the carotid body tumor, and two patients had common carotid artery-internal carotid artery artificial vascular reconstruction. RESULTS: No perioperative mortality or stroke occurred. The mean blood loss was 455 (range, 250-650) mL. Two patients had pseudoaneurysm or vocal cord paralysis postoperatively and recovered with stent graft implantation and medical treatment, respectively. The patients were followed for 6 to 17 (mean, 11) months, with no recurrence observed. CONCLUSION: Surgical treatment of a carotid body tumor is acceptably safe and effective according to Shamblin classification. Pseudoaneurysm can occur after blunt dissection of the tumor and can be treated with a stent graft.

Expression of beclin 1 in non-small cell lung cancer: an immunohistochemical study.

BACKGROUND: Cigarette smoking causes a variety of adverse human health effects, including lung cancer. The molecular events associated with smoke-induced carcinogenesis are thought to be related in part to autophagy. Beclin 1 is an important autophagy-related protein involved in cell death and cell survival. AIM: The purpose of this investigation was to determine the beclin 1 protein and its association with cigarette smoke and the mutation of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). MATERIAL AND METHODOLOGY: Our study included 108 cases of non-small cell lung cancer who were admitted in our hospital. The beclin 1 protein was detected by immunohistochemistry and EGFR mutation by direct sequencing. RESULTS: Beclin 1 expression could be detected in 15 (13.9%) of 108 specimens. These studies investigated that beclin 1 expression was associated with heavy smoking, the gender and the histological type of NSCLC (P = 0.023, 0.035 and 0.039). No association of beclin 1 with EGFR mutation was found (P > 0.05). CONCLUSION: The results from these experiments indicate that heavy smoking may induce the beclin 1 protein in NSCLC.

Prognosis of eight Chinese cases of primary vaginal yolk sac tumor with a review of the literature.

BACKGROUND: Primary vaginal yolk sac tumor is a rare malignancy in the pediatric population, and a diagnostic challenge and appropriate initial treatment remains unsolved. The aim of this study was to investigate the clinicopathologic features, treatment and prognosis of this tumor. MATERIALS AND METHODS: Eight cases of primary vaginal yolk sac tumor were reported with a literature review. RESULTS: There were 4 pure yolk sac tumor cases and four mixed germ cell tumors containing yolk sac tumor element, including two cases with embryonal carcinoma and two cases with embryonal carcinoma and dysgerminoma. Partial vaginectomy was performed in four cases and all patients received chemotherapy. 85 cases in literatures were reviewed and 9 cases were misdiagnosed. Follow-up data was available in 77 cases and 5-year overall survival rate was 87.6%. 5-year survival rate of biopsy with chemotherapy, conservative surgery with chemotherapy and radical surgery with chemotherapy was 91.1%, 100% and 28.6%, respectively (p<0.001). Compared to cases without relapse or metastasis after initial treatment, patients with relapse or metastasis had a shorter overall survival (35.6% vs 96.6%, p<0.001). CONCLUSIONS: Mixed germ cell tumor containing yolk sac tumor element was not uncommon and partial vaginectomy may be a good choice for primary vaginal mixed yolk sac tumor type to eradicate local tumor cells and provide complete information for pathological diagnosis and postoperative adjuvant therapy.

CD44v3 and VEGF-C expression and its relationship with lymph node metastasis in squamous cell carcinomas of the uterine cervix.

BACKGROUND: To investigate the expression of CD44v3 and vascular endothelial growth factor-C (VEGF-C) and their relationship with lymph node metastasis in squamous cell carcinomas (SCC) of the uterine cervix. MATERIALS AND METHODS: Expression of CD44v3 and VEGF-C was analyzed in 109 cases of cervical SCC by immunohistochemistry (IHC). The relationship was analyzed between expression and the patient age, histological differentiation, formation of tumor emboli in lymphoid vessels, lymph node metastasis, FIGO staging, and TNM classification. RESULTS: Expression rates for both CD44v3 and VEGF-C were 43.1% in cervical SCC. The cells with positive immunohistochemical staining of CD44v3 were distributed mainly around the keratin pearls in well differentiated carcinomas, but distributed diffusely in the moderately and poorly differentiated lesions. VEGF-C was found stained positively in most of the tumor cells. There were differences in expression between normal epithelium and atypical hyperplasia as well as carcinoma. Both CD44v3 and VEGF-C were found to be associated positively with lymph node metastasis and TNM classification (both p=0.000). Neither CD44v3 nor VEGF-C was found to be associated with patient age, histological differentiation, formation of tumor emboli in lymphoid vessels and FIGO staging. CD44v3 was found to be associated with VEGF-C positively (p=0.000). CONCLUSIONS: Abnormal expression of CD44v3 and VEGF-C is associated closely with the lymph node metastasis in cervical SCC, and these agents may cooperate in carcinogenesis and development of metastatic lesions.

Does HBV infection increase risk of endometrial carcinoma?

OBJECTIVE: Connections between chronic inflammation and tumor development and progression are now generally accepted. Recent evidence indicates that hepatitis B is associated with several types of cancer, but whether endometrial carcinoma (EC) is included has not been reported. METHODS: We analyzed HBV serum marker status in 398 patients with endometrial cancer, comparing them to 788 control women undergoing health examination. RESULTS: The total prevalence of HBsAg tested positive in cancer group was significantly higher than the control group (12.8% vs 6.0%, P=0.001), while positive HBsAb was significantly lower (41.2% vs 68.5%, P=0.001). Hepatitis B carriers in endometrial cancer group were also more frequent than in the control group (9.3% vs 5.5%, P=0.013). Interestingly, in the endometrial cancer group, 147 cases were HBV serum marker negative, which was also higher than in the control group (36.9% vs 15.6%, P=0.001). CONCLUSION: There may be a correlation between HBV infection and endometrial carcinoma.

Concomitant lymphocyte-rich classical Hodgkin's lymphoma and Warthin's tumor.

Lymphomas associated with Warthin's tumor (WT) are extremely rare. Here, we report the simultaneous occurrence of lymphocyte-rich classical Hodgkin's lymphoma (LRCHL) and WT in a 78-year-old patient whose symptoms included an enlargement of the left parotid gland. Upon parotidectomy, the tissue specimen showed a WT with extensive replacement of the lymphoid stroma by small lymphocytes and some scattered Reed-Sternberg cells; however, the oncocytic epithelium was preserved. Further investigation revealed mediastinal and abdominal lymphadenopathy, consistent with stage IVB disease. To our knowledge, this is the first case report of LRCHL associated with WT. The lymphoid stroma in WT is part of the systemic lymphoid tissue and thus may be involved in the dissemination of the lymphoma. This case serves as a reminder that a careful evaluation of the histomorphological and immunohistological features of the lymphoid tissue is required for a WT biopsy.

Tumor-associated macrophages correlate with progesterone receptor loss in endometrial endometrioid adenocarcinoma.

AIM: It has been well established that tumor-associated macrophages (TAMs) play a tumor promoting role in endometrial endometrioid adenocarcinoma (EEC). But the association with TAMs and sex hormone receptor expression, and progression of precancerous endometrial lesions in EEC has been little reported. MATERIAL AND METHODS: We used immunohistochemistry to examine the expression of CD68, CD34, vascular endothelial growth factor (VEGF), estrogen receptor (ER) and progesterone receptor (PR) in 95 cases of EEC, as well as 35 cases of endometrial hyperplasia (including 15 atypical hyperplasia, 10 complex hyperplasia and 10 simple hyperplasia). We also correlated TAMs count with various clinicopathological factors, sex hormone receptor, and prognostic value in patients with EEC. RESULTS: We identified that TAMs count increased linearly with disease progression (mean count per case at × 200 magnification: simple hyperplasia, 6.30; complex hyperplasia, 11.20; atypical hyperplasia, 29.40; EEC 55.81, respectively; P < 0.001), that microvascular density (MVD) also increased accordingly (27.50, 30.20, 50.13 and 59.94, respectively; P < 0.001). The expression of progesterone receptor, not of estrogen receptor, significantly decreased with disease progression (P < 0.05). Moreover, histopathologic grades, International Federation of Gynecology and Obstetrics (FIGO) stage (2009), depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, and expression of PR and VEGF were associated with TAMs count (P = 0.0001, P = 0.004, P = 0.0001, P = 0.04, P = 0.0001, P = 0.0001, P = 0.0001, respectively). Progesterone receptor expression was also associated with histopathologic grades, lymphovascular space invasion, VEGF and high TAMs (P = 0.035, P = 0.022, P = 0.014, P = 0.001, respectively). The estimated 5-year survival rate of patients with low TAMs was significantly higher than those with high TAMs (96.4% vs 69.8%, P = 0.002). CONCLUSION: TAMs are potentially related to PR loss and progression of precancerous endometrial lesions in EEC.

Prediction value of XRCC 1 gene polymorphism on the survival of ovarian cancer treated by adjuvant chemotherapy.

OBJECTIVE: We conducted a prospective study to test the association between three amino acid substitution polymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1 (Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. METHODS: 195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in our study. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conducted by TaqMan Gene Expression assays. RESULTS: The XRCC1 194 Trp/Trp genotype conferred a significant risk of death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, those carrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/ Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). CONCLUSION: This study is the first to provide evidence that XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovarian cancer cases undergoing adjuvant chemotherapy.

Tumor-associated macrophages, epidermal growth factor receptor correlated with the triple negative phenotype in endometrial endometrioid adenocarcinoma.

It has been well established that tumor-associated macrophages (TAMs) play a tumor-promoting role in endometrial endometrioid adenocarcinoma (EEC). However, the association with TAMs and the triple-negative phenotype (TNP) in EEC has not yet been reported. We used immunohistochemistry to examine the expression of CD68, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in 186 cases of EEC. Fluorescent in situ hybridization (FISH) was also used for HER2 amplification, and the association with TAMs count, EGFR expression, and triple-negative phenotype was analyzed. Twenty-eight of 186 patients (15.05%) had the TNP. It was associated with advanced stage disease (P<0.0001), high grade disease (P<0.0001), depth of myometrial invasion (P=0.003), pelvic lymph node metastasis (P<0.001), lymphovascular space invasion (P=0.001), and EGFR expression (P=0.032). Margin TAMs count was also significantly increased in the TNP-positive group, the EGFR-positive group, and the PR-negative group (P<0.001, respectively). The TNP was associated with a significantly worse overall survival (OS) (log rank test, P=0.018). The estimated 5-year OS of patients with TNP was 59.1%, while that without TNP was 78.5%. Multivariate analysis showed high margin TAMs, and the histopathological grades were significantly associated with OS. The TNP in EEC is associated with poor prognostic surgical-pathological factors, worse prognosis, as well as with high margin TAMs and overexpression of EGFR, which may serve as potential targeted therapies for the special phenotype in EEC.

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.

Primary adenoid cystic carcinoma of sweat glands in vulva: report of an unusual case and review of the literature.

Adenoid cystic carcinoma arising from the vulvar sweat glands is a rare malignancy of the female genital tract. We report a case of adenoid cystic carcinoma of sweat glands occurring in the left labia majora of a 52-year-old female patient. The patient underwent radical hemivulvectomy and left inguinal lymph node dissection with negative surgical margins and negative inguinal lymph node metastasis. Then, four episodes of combined chemotherapy without further radiotherapy were given. However, the tumor recurred after 3 months. Currently, the patient has been followed up for 2 years with no distant metastasis. According to our experience, although the tumor has a high tendency of local recurrence after resection, an acceptable survival time of the patient can be achieved with primary surgery.

Expression and significance of Cyr61 in distant metastasis cells of human primary salivary adenoid cystic carcinoma.

OBJECTIVE: The objective of this study was to examine the expression of cysteine-rich protein 61 (Cyr61) in the distant metastatic tumor cells of human primary salivary adenoid cystic carcinoma (SACC) and its relationship with tumor angiogensis and metastasis. STUDY DESIGN: The experimental group comprised 35 paraffin-embedded tumor specimens of distant metastasis from primary SACC, with their corresponding primary tumor tissues and matched normal salivary gland tissues used as the control groups. Immunohistochemical staining was used to detect the expression of Cyr61 and vascular endothelial growth factor in the experimental and control groups. Vascular endothelial cells were highlighted by the anti-CD34 antibody, and the Weidner method was used to quantify microvessel density (MVD). RESULTS: Cyr61 was overexpressed in distant metastatic tumor cells of primary SACC. Positive expression of Cyr61 and vascular endothelial growth factor (VEGF) progressively increased in normal salivary gland tissues, primary tumor tissues, and tumor tissues of distant metastasis (P < .05). Compared with primary tumor tissues, Cyr61 expression and VEGF expression showed significant increase in tumor tissues of distant metastasis (P < .05). Cyr61 expression significantly correlated with VEGF expression and MVD (P < .05). CONCLUSIONS: Cyr61 appeared to have a significant association with tumor angiogenesis and metastasis in SACC and may be an important target in tumor antiangiogenesis therapy.

Expression of Cyr61 in primary salivary adenoid cystic carcinoma and its relation to Ki-67 and prognosis.

Cysteine-rich protein 61 (Cyr61) selectively binds heparin and insulin-like growth factors and mediates a variety of biological actions, including cell adhesion, differentiation, proliferation, migration, angiogenesis, and tumorigenesis. Cyr61 is also a prognostic factor for tumor progression and survival of individuals with various types of tumors. This study investigated the relationship between the expression level of Cyr61 and clinicopathological features, as well as the prognostic significance of Cyr61 expression in human salivary adenoid cystic carcinoma (SACC). The expression of Cyr61 and Ki-67, a cell-proliferation marker, was examined immunohistochemically in paraffin embedded tissue specimens from 60 SACC patients who underwent radical surgery between 1995 and 2004. A chi-square test was used to investigate the relationship between Cyr61 and Ki-67 expression and clinicopathological features. Survival analysis was performed to determine the prognostic significance of Cyr61 expression. Cyr61 expression was observed in 39 cases (39/60, 65%) of SACC, and Cyr61 expression was positively correlated with Ki-67 expression (P=0.002). A high expression of Cyr61 was significantly associated with solid subtype, perineural invasion, vascular invasion or cancer embolus, advanced stage, recurrence, and metastasis (P<0.05). The survival rate of patients with high expression of Cyr61 or Ki67 was significantly lower than that of patients with low expression. Multivariate Cox's proportional hazards analysis showed that vascular invasion, TNM stage, recurrence, distant metastasis, Ki-67 expression, and Cyr61 expression were independent prognostic factors of overall survival (P<0.05). Cyr61 expression is significantly correlated with Ki-67 expression and may have potential value in screening high-risk cases for recurrence and metastasis, as well as identifying poor prognosis in SACC patients.