Pattern Of Tumor Invasion Research Articles

Overexpression of ZDHHC14 promotes migration and invasion of scirrhous type gastric cancer.

Scirrhous type gastric cancer is highly aggressive and has a poorer prognosis than many other types of gastric carcinoma, due to its characteristic rapid cancer cell infiltration and proliferation, extensive stromal fibrosis, and frequent peritoneal dissemination. The aim of the present study was to identify novel prognostic markers or therapeutic targets for scirrhous type gastric cancer. We reviewed a list of genes with upregulated expression in scirrhous type gastric cancer and compared their expression with that in normal stomach from our previous Escherichia coli (E. coli) ampicillin secretion-trap (CAST) analysis. We focused on the ZDHHC14 gene, which encodes zinc finger, DHHC-type containing 14 protein. qRT-PCR analysis of ZDHHC14 in 41 gastric cancer cases revealed that compared to mRNA levels in normal non-neoplastic gastric mucosa, ZDHHC14 mRNA was overexpressed in 27% of gastric cancer tissue samples. The overexpression of ZDHHC14 was significantly associated with depth of tumor invasion, undifferentiated histology and scirrhous pattern. The invasiveness of ZDHHC14-knockdown HSC-44PE and 44As3 gastric cancer cells was decreased in comparison with that of the negative control siRNA-transfected cells, together with downregulation of MMP-17 mRNA. Integrins α5 and β1 were also downregulated in ZDHHC14-knockdown 44As3 cells. Forced expression of ZDHHC14 activated gastric cancer cell migration and invasion in vitro. These results indicate that ZDHHC14 is involved in tumor progression in patients with scirrhous type gastric cancer.

Simultaneous resection of abdominal cancer and synchronous pancreaticoduodenal metastasis: Indications and literature review

This study was aimed to identify the potential indications for simultaneous resection of abdominal cancer and synchronous pancreaticoduodenal metastasis (SRAPM) and improve the efficacy of SRAPM. The data of 34 patients who underwent SRAPM were retrospectively reviewed. The intraoperative findings, morbidity and mortality, patterns of tumor invasion in the pancreas and duodenum, lymph node metastases, long-term outcomes and causes of death were evaluated. Fourteen patients (41.2%) developed complications, and 2 died of pancreatic fistulas with abdominal bleeding. The in-hospital mortality was 5.9%. The overall 1-year, 2-year and 3-year survival rates were 52.9%, 32.3% and 21.8%, respectively. The survival rates depended on the primary tumor, the invasion pattern, the presence of metastatic lymph nodes at the paraaortic site and the presence of residual tumor. The follow-up outcomes revealed that the main causes of death were as follows: systemic metastasis (n = 7), peritoneal metastasis (n = 6) and intrahepatic metastasis (n = 6). SRAPM is indicated for low-grade malignant tumors and in cases with direct invasion of the pancreaticoduodenum. The presence of metastatic lymph nodes at the paraaortic site, intrahepatic metastasis, micro-peritoneal metastasis, and distinct metastasis should be contraindications for the surgical procedure.

Abstract 4326: The potential role of IMP-3 and PDPN in invadopodia formation and collective cancer invasion: Anti-invadopodia therapy as a therapeutic target

Abstract Better understanding the mechanisms underlying the metastatic process is essential to developing novel targeted therapeutics. Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are actin-rich structures that have the ability to degrade the underlying extracellular matrix (ECM) and promote cell invasion. However, many questions concerning the mechanisms of invadopodia formation, regulation and function remain open to debate. Meanwhile, invasion of cells into the surrounding tissue and destruction of normal tissue architecture are two hallmarks of malignant tumors. Morphologically, two patterns of tumor invasion can be distinguished; single cell and collective cell invasion. The invasion of single cells and collective cells is often correlated with dramatic changes in the expression and function of adhesive and regulatory proteins. These changes are reminiscent of early developmental processes when cells acquire a migratory, mesenchymal phenotype. Currently, the role of invadopodia in collective cancer invasion is completely unknown. In the present study, we reveal that insuline-like growth factor-II mRNA-binding protein-3 (IMP-3) associated with invadopodial infiltration and collective cancer invasion through podoplanin (PDPN) mRNA stabilization as a component of invadopodia, suggesting that invadopodia plays a pivotal role in invasive front of collective cancer invasion and thereby involved the cancer metastasis. This finding, combined with other investigations into the mechanisms of invadopodia formation, reveal clinically-relevant targets for intervention in invadopodia, including IMP-3 and PDPN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4326. doi:1538-7445.AM2012-4326

The importance of stromal inflammation in squamous cell carcinoma of the tongue

Histological risk assessment evaluating worst pattern of tumour invasion (WPOI), and lymphocytic response (LR), has previously been shown to be of prognostic significance in squamous cell carcinomas of the head and neck (SCCHN). SCCHN is a heterogeneous group of tumours including tumours located in the oral cavity, of which the majority is located in the tongue. Haematoxylin/eosin-stained slides from diagnostic biopsies from 94 cases of SCC on the tongue were evaluated for WPOI and LR. Within the inflammatory infiltrate, the percentage of eosinophilic granulocytes was also estimated. Results were correlated with clinical data such as response to treatment and recurrence. For WPOI the majority of patients, 84%, showed small invasive tumours islands with a size <15 cells (grade 4). No correlation with survival, response to treatment or recurrence was seen for WPOI. More than half of the patients showed a dense lymphocytic infiltrate, a factor that was significantly correlated with complete response to radio therapy. Of the patients with dense lymphoid infiltrate, the majority, 63%, did not either have a recurrence. No significant correlation with recurrence, response to treatment or any other factor was seen for presence of eosinophils. Data clearly showed that tongue tumours have a split invasive growth pattern and an intense inflammatory response at the tumour interface. Results also indicated that evaluation of the intensity of the inflammatory infiltrate at the tumour interface in tongue SCC could provide information of potential importance for choice of treatment and prognosis.

Patterns of cancer invasion revealed by QDs-based quantitative multiplexed imaging of tumor microenvironment

Tumor growth and progression depends on their microenvironment, which undergoes constant co-evolution because of the dynamic tumor–stormal interactions. Such co-evolution has long been under appreciated due to the lack of appropriate technology platforms to simultaneously reveal these complex interactions. Here we report on a quantum dots based multiplexed imaging and spectrum analysis technology to simultaneously study major components of tumor stroma, including type IV collagen, tumor angiogenesis, macrophages infiltration and tissue destructive proteolytic enzyme matrix metalloproteinase 9. The new technology revealed a panoramic picture of the tempo-spatial co-evolution of tumor cells and their stroma at the architecture level. Four patterns of tumor invasion with distinctive co-evolution features were identified as Washing pattern, Ameba-like pattern, Polarity pattern and Linear pattern. This quantum dots based multiplexed technology could help gain new insight into the complex process of tumor invasion, and formulate new anti-cancer strategies.

Oscillatory dynamics in a model of vascular tumour growth - implications for chemotherapy

BackgroundInvestigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth.ResultsBy analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type) dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls.ConclusionsWe have developed a mathematical model of vascular tumour growth formulated as a system of partial differential equations (PDEs). Employing a combination of numerical and analytical techniques, we demonstrate how the spatio-temporal dynamics of the untreated tumour may influence its response to chemotherapy.ReviewersThis manuscript was reviewed by Professor Zvia Agur and Professor Marek Kimmel.

Dual-color fluorescence imaging in a nude mouse orthotopic glioma model

We sought to establish a new orthotopic glioma model of nude mice by transfer of DsRed2, a red fluorescent protein gene, to malignant glioma cells and to perfuse the tissue with fluorescein isothiocyanate (FITC) dextran in vivo, which would permit the concurrent detection of brain tumor invasion and angiogenesis in vivo by florescence microscopy. 9L or U87 malignant glioma cells with DsRed2 expression were intracerebrally injected into the nude mice. FITC-dextran was administered intravenously to the mice bearing DsRed2-9L or DsRed2-U87 cells immediately before they were sacrificed at 10 days or 15 days after the implantation, respectively. Coronal vibratome sections were examined using 2D and 3D fluorescence microscopy and the results were compared with those examined by routine hematoxylin and eosin (H & E) staining. Angiogenesis induced by glioma was confirmed by two-dimensional and three-dimensional imaging analysis. DsRed2 fluorescence clearly demarcated the primary tumor margins and readily allowed for the visualization of local invasion at the single-cell level in the brain adjacent to tumor. We found that a few tumor cells migrated from the tumor mass along the aberrant microvasculature, but did not extend out of the angiogenic areas. However, locally invasive foci were very difficult to detect by H & E staining. We demonstrated, for the first time, that abnormal vascular structure and glioma cells can be visualized concurrently by fluorescence microscopy. This method is superior to H & E staining for the detection and study of physiologically relevant patterns of brain tumor invasion and angiogenesis in vivo.

Association of tumor satellite distance with prognosis and contralateral neck recurrence of tongue squamous cell carcinoma

The margin status is an important prognosticator for the survival of patients with tongue cancer. Although a positive margin is associated with a poor prognosis, those with clear margins do not always have good clinical outcomes. We investigated the margin status, pattern of tumor invasion (POI), and tumor satellite distance (TSD) in 119 freshly treated tongue cancers and assessed their association with the characteristics and clinical outcomes. A close or clear margin and POI were not associated with overall survival. Tumor satellites occurred in 92% of tumors and were significantly associated with betel nut exposure. Patients with TSD <or=0.5 mm had significantly better overall survival. Patients with TSD >0.5 mm had a higher incidence of local recurrence, shorter intervals to neck recurrence, and a higher propensity to contralateral or bilateral cervical nodal metastasis. TSD is associated with local recurrence, contralateral neck metastasis, and the overall survival of patients with tongue cancer.

Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma?

Since 5-fluorouracil (5-FU)-based chemotherapy has become standard adjuvant treatment for patients with node-positive colonic adenocarcinoma, there has arisen the need for predictive factors. Thymidylate synthase (TS) is a major target of 5-FU's action, and high TS expression in carcinoma cells could reduce its cytostatic effect. Both, a 28-base pair repeat polymorphism and a cytosine vs. guanine single nucleotide polymorphism in the promoter region of the TS gene are known to modulate its expression. All patients with a single, non-metachronous node-positive colonic adenocarcinoma who underwent a potentially curative resection at this institution in the years 1994-2002, and who received adjuvant 5-FU (n=95) were included in this study. Ninety-four of the 95 patients were successfully genotyped: 70 patients were classified as TS gene low-expressors (2R-2R, 2R-3C and 3C-3C), and 24 patients were classified as high-expressors (2R-3G, 3C-3G and 3G-3G). Contrary to the hypothesis, Kaplan-Meier survival analysis did not reveal any differences between the groups (power of 0.8 to detect an absolute survival difference >30%). In a Cox model, venous angioinvasion and the infiltrative pattern of tumour invasion were strong adverse factors. These results argue against a practical role for the TS gene repeat polymorphism or the C/G single nucleotide polymorphism as a predictive factor. However, by careful histopathological examination a high-risk group of node-positive patients can be defined that could be candidates for studies of alternative (more aggressive) adjuvant treatment.

The Impact Factors on Prognosis of Patients With pT3 Upper Urinary Tract Transitional Cell Carcinoma

Stage 3 upper urinary tract transitional cell carcinoma is a heterogeneous disease including different tumor locations (pelvis vs ureter) and invasion patterns (renal parenchyma, peripelvic fat and periureteral fat). Unfortunately the outcomes of patients with pT3 disease with different invasion pattern are largely unknown. This study presents the clinical outcome of patients with pT3 disease with upper urinary tract transitional cell carcinoma. We retrospectively reviewed the medical records of all patients with pT3 disease with upper urinary tract transitional cell carcinoma. Four patient groups were classified according to tumor location and tumor invasion pattern. Prognostic factors including age, gender, tumor grade, tumor size, tumor number, tumor location and microscopic finding of vascular invasion were analyzed with respect to disease recurrence and survival. A total of 72 patients were included in this study. The most common complaint and tumor relapse pattern were painless gross hematuria and distant metastasis, respectively. Patients with pT3 disease with superficial parenchymal invasion had better disease-free and recurrence-free survival than the other 3 groups. Initial tumor location (p = 0.02) and vascular invasion (p = 0.02) were independent factors for disease-free survival, and vascular invasion (p = 0.001) was the only predictive factor for recurrence-free survival. The present study demonstrated that patients with pT3 disease with superficial parenchymal invasion should be considered to have lower stage disease, and that vascular involvement is the only independent prognostic factor for patients with pT3 disease for disease-free and recurrence-free survival. Systemic adjuvant therapy should be recommended for patients with pT3 disease with vascular involvement.

The expression of metaloproteinases-2 and -9 is different according to the patterns of growth and invasion in squamous cell carcinoma of the penis

Squamous cell carcinoma (SCC) of the penis is characterized by different patterns of growth and local invasion. The matrix metalloproteinases (MMPs) is a family of proteolytic enzymes that are involved in the degradation of extracellular matrix to allow the migration of tumor cells. The present study examined whether the expression of MMP-2 and -9 is correlated with the patterns of tumor growth and invasion in penile SCC. The expression of MMP-2 and -9 was examined immunohistochemically in samples of 115 patients. The cases were divided in three groups according to the patterns of growth and invasion: group 1, exophytic growth and pushing pattern of invasion; group 2, endophytic growth and invasion in large sheets of cells; and group 3, endophytic growth and invasion in small group or isolated cells. Tumors with MMP-2 and -9 overexpression are deeply invasive and present an invasion pattern of small groups of cells. Also, expression of MMP-2 changed from membrane to cytoplasm in invasive tumors, maybe representing activation of MMP-2. These findings allow us to conclude that the less differentiated tumors, which are more invasive and with a pattern of invasion in small group of cells, are associated with the overexpression of MMPs.

Tumor-invasion pattern: a new prognostic factor in penile carcinoma?

Tumor-invasion pattern: a new prognostic factor in penile carcinoma?

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/ISUP 1998 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.

3-D tumor invasion pattern analysis of cervical carcinoma

5130 Background: A high-resolutional (10μm) reconstruction of the 3-D tumor invasion of squamous cell carcinoma of the uterine cervix has become feasible for the first time using a newly developed ...

The influence of the pattern of mandibular invasion on recurrence and survival in oral squamous cell carcinoma.

Controversy exists over the predictive value of the presence and pattern of tumor invasion of the mandible in oral squamous cell carcinoma (SCC). Many authors have questioned increasing the classification of small tumors to T4 on the basis of mandibular invasion alone. There are little data on the influence of the pattern of invasion on prognosis. We prospectively reviewed 100 consecutive mandibular resections for previously untreated oral SCC. Clinical and pathologic data collected included details of soft and hard tissue histologic findings. Outcomes included recurrence (local, regional, and distant metastases), disease-specific survival, and death from other causes. The median follow-up for survivors was 65 months. Of 100 cases, 65 involved segmental and 35 involved marginal resections. Sixty-two percent of mandibles were invaded by tumor. Local recurrence occurred in 21% and was strongly correlated with tumor size, nodal involvement, and pattern of soft tissue invasion. The 5-year disease-specific survival was 68%, and the crude survival was 50%. Mandibular invasion predicted for recurrence and disease-specific survival, even after correcting for the effects of other variables. The pattern of mandibular invasion (erosive/infiltrative) was also predicted for recurrence and disease-specific survival. Even in the presence of mandibular invasion, soft tissue factors are the most important determinants of prognosis. Upstaging tumors on the basis of mandibular invasion is justified. An infiltrative pattern of bone invasion is a marker of aggressive tumor biology and should be included in the pTNM classification.

Heparanase and tumor invasion patterns in human oral squamous cell carcinoma xenografts.

The role of heparanase, an endo-beta-glucuronidase specifically degrading heparan sulfate (HS) glycosaminoglycans, in the mechanism of cancer cell invasion was investigated. Three human oral squamous cell carcinoma (SCC) cell lines (i.e., HSC-2, HSC-3 and LMF4), exhibiting various degrees of invasiveness to their surrounding tissues, were xenografted to the tongue of SCID mice in order to establish experimental cancer foci. Cancer cells and their surrounding tissues were examined for the expression of heparanase mRNA by an in situ hybridization technique, and for various basement membrane (BM)-associated molecules (i.e., perlecan, laminins and type IV collagen) by immunohistochemical procedures. BM structures surrounding cancer tissues were also examined by electron microscopy. Increasing levels of heparanase mRNA expression were observed with the progression of cancer invasiveness, as manifested by the destruction of BM structures. Enhanced heparanase enzyme activities in cancer tissues with more invasive properties were demonstrated by the disappearance of HS glycosaminoglycans in the face of retained HS proteoglycan core proteins. These results demonstrated a positive correlation between the heparanase enzyme activities and the invasiveness of human oral SCC. The roles of heparanase in cancer cell invasion were not precisely clarified by the present morphological study, but the enhanced heparanase activity in an early phase of BM destruction by cancer cells suggested the participation of this enzyme from the early phase of cancer invasion.

Tumor and tumor-like lesions of duodenum: CT and barium imaging features

Neoplasms of the duodenum, either primary or secondary, are uncommon. However, imaging diagnosis for presurgical evaluation is extremely important due to complex regional anatomy. Computed tomography (CT) and barium-based double contrast examination (UGI series) are most frequently employed to evaluate the tumor invasion and intraluminal mucosal pattern. In this pictorial review, the CT and UGI series imaging features of benign and malignant duodenal tumors and tumor-like lesions are demonstrated and discussed.

Invasive front grading: reliability and usefulness in the management of oral squamous cell carcinoma.

The value of histological grading was examined with emphasis on reliability of assessment in 102 cases of intraoral squamous cell carcinoma from Northern Ireland with known outcome. Two pathologists independently graded the invasive tumour front blinded to the stage and outcome. Intraobserver agreement was acceptable but interobserver agreement was not satisfactory. The degree of keratinisation was assessed most consistently while nuclear polymorphism was the least reliable feature. Multivariate survival analysis showed that the total grading score was associated with overall survival while the pattern of tumour invasion was the most valuable feature in estimating regional lymph node involvement. The number of positive lymph nodes was strongly associated with regional relapse, while the treatment modality and status of the surgical margins correlated with local relapse. Grading of selected features in OSCC is reliable and can facilitate treatment planning.

Patterns of invasion and routes of tumor entry into the mandible by oral squamous cell carcinoma.

An understanding of the patterns, spread, and routes of tumor invasion of the mandible is essential in deciding the appropriate level and extent of mandibular resection in oral squamous cell carcinoma. A prospective study of histologic patterns of tumor invasion and routes of tumor entry into the mandible was performed in a consecutive series of 100 previously untreated patients. The pattern of tumor invasion of the mandible depended on the depth of invasion both in the hard (p =.001) and soft tissues (p =.001). There was evidence that the pattern of invasion was related to histologic prognostic indicators of the disease, such as extracapsular spread from invaded lymph nodes (p =.03). The route of tumor entry was at the point of abutment to the mandible (direct) in all 13 cases, invading the dentate part of the mandible. Fifty-five percent (23 of 42) of tumors invading the edentulous ridge entered through the occlusal (superior) surface. Direct entry to the mandible in the edentulous ridge was more likely for tumors arising in the tongue, floor of the mouth and the buccal mucosa compared with alveolar or retromolar sites (p =.003) Larger or more deeply invading tumors in the soft tissue are more likely to invade the mandible and show the more aggressive (invasive) form of tumor spread, reducing the options of a more conservative (rim) resection. Tumors tend to enter the mandible at the point of abutment, which in both the dentate and edentulous jaw is often at the junction of the reflected and attached mucosa. A point of tumor entry below the occlusal ridge or gingival crest should be assumed when planning rim or marginal resections of the mandible.

下顎骨切除法別にみた下顎歯肉へん平上皮癌の顎骨浸潤に関する臨床・病理組織学的検討

We assessed the relation between the procedure used for mandibular resection and the pattern of tumor invasion to the jaw in 176 patients with lower gingival carcinoma at the First Department of Oral & Maxillofacial Surgery, Tokyo Dental College from 1988 through 1998. The results were as follows: 96 patients (55%) received marginal resection of the mandible, 74 (42%) received segmental resection of the mandible, and 6 received hemimandibulectomy. The tumors in the patients who underwent marginal reresection were classified into two categories: invasion to the periostium (11 patients, 11%) and invasion to the cortical bone and marrow (23 patients, 24%). The tumors in the patients who underwent segmental resection were classified into two categories: invasion to the periostium (48 patients, 65%) and invasion to the cortical bone and marrow (26 patients, 35%). Local recurrence (soft tissue) occurred in 14 of the 80 (18%) patients who underwent segmental mandibulectomy patients and in 14 of the 96 (14%) who underwent marginal mandibulectomy.