Primary Tumor Area Research Articles

Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT), in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.

Localized experimental bone metastasis drives osteolysis and sensory hypersensitivity at distant non-tumor-bearing sites.

Patients with breast cancer metastasis to bone suffer from inadequate pain relief. Animal models provide increased understanding of cancer-induced bone and sensory alterations. The objective of this study was to investigate the measures of pain at distant non-tumor-bearing sites in animals with localized bone metastasis. Immunocompetent BALB/c mice are injected intra-tibially with murine mammary carcinoma cells (4T1) or saline, and the sensitivity to mechanical and thermal stimuli in the contralateral paw was examined. In addition to previously demonstrated development of osteolysis and hypersensitivity to mechanical and thermal stimuli in the cancer-injected tibia, these animals exhibited an increase in sensory hypersensitivity in the contralateral limb. No bone lesions were evident on radiographs of the contralateral limbs. Histomorphometry detected decreased bone volume per tissue volume and increased osteoclast number in the contralateral tibia and vertebral bones of cancer-bearing animals. Neuroplasticity was examined by immunofluorescence for calcitonin gene-related peptide (CGRP) in sensory neurons and glial fibrillary acidic protein (GFAP) in lumbar spinal cords. CGRP-immunoreactivity and GFAP-immunoreactivity were significantly elevated both ipsilateral and contralateral in tumor-bearing animals. The anti-inflammatory and osteolysis-targeting drug rapamycin reduced hypersensitivity to mechanical and cold stimuli, attenuated GFAP over-expression, and lowered osteoclast number. The osteoclast-targeting drug pamidronate reduced sensitivity to cold and protected against bone loss. Localized bone cancer drives hypersensitivity, bone remodeling, and sensory neuron plasticity at sites distant from the primary tumor area. Drugs targeting these mechanisms may be useful in the treatment of pain distant from the primary tumor site.

Intratumoral heterogeneity of cancer driver genomic alterations across several tumor types.

1558 Background: Intratumoral heterogeneity (ITH) or variations in genomic alterations (GA) between different areas of primary tumors or in their metastases has been an area of intense investigatio...

Molecular Heterogeneity in Primary Breast Carcinomas and Axillary Lymph Node Metastases Assessed by Genomic Fingerprinting Analysis.

Molecular heterogeneity within primary breast carcinomas and among axillary lymph node (LN) metastases may impact diagnosis and confound treatment. In this study, we used short tandem repeated sequences to assess genomic heterogeneity and to determine hereditary relationships among primary tumor areas and regional metastases from 30 breast cancer patients. We found that primary carcinomas were genetically heterogeneous and sampling multiple areas was necessary to adequately assess genomic variability. LN metastases appeared to originate at different time periods during disease progression from different sites of the primary tumor and the extent of genomic divergence among regional metastases was associated with a less favorable patient outcome (P = 0.009). In conclusion, metastasis is a complex process influenced by primary tumor heterogeneity and variability in the timing of dissemination. Genomic variation in primary breast tumors and regional metastases may negatively impact clinical diagnostics and contribute to therapeutic resistance.

The efficacy of delayed surgery in children with high-risk neuroblastoma.

Surgery is an important part of treatment in children with neuroblastoma; however, exact timing is unclear. Both initial and delayed surgery was suggested as the best by numerous studies. Thus, we aimed to investigate the role of delayed surgery on 31 children with high-risk neuroblastoma. Thirty-one children with high-risk neuroblastoma were enrolled into the study. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) for windows 10.0. There 'were 15 male and 16 female patients with a median age of 3.0 ± 3.2 years. Primary tumor site was adrenal in 27, non-adrenal in two, pelvic in one, and mediastinal in one patient. MYCN gene was amplified in four and non-amplified in 11 children on totally 15 children with available data. Lactate dehydrogenase was elevated in 30 children. The tumor volumes at diagnosis and before surgery in the whole group were 154.3 and 12.5 mL, respectively. The decline in tumor volume was statistically significant (P < 0.0001). Initial surgery was performed in three and delayed in 20 children, and eight children were inoperable. Surgical complication rate was 66.6% (two out of three patients) in initial surgery group; however, the rate was 15% (3 out of 20 patients) in delayed surgery group. The 5-year event-free survival and overall survival rates in the whole group were 44.8% and 50.8%, respectively. Primary tumor area control rate was 95% In conclusion, the delayed surgery with intensive chemotherapy and radiotherapy has been successful for primary control in high-risk neuroblastoma patients.

Infiltration of CD8+ lymphocytes is an independent prognostic factor of biochemical failure-free survival in prostate cancer.

The adaptive immune system can potentially have dual roles in cancer development and progression by contributing to or suppressing tumor progression and metastasis. The aim of this study was to evaluate the prognostic impact of adaptive immune cells residing in different tumor compartments in prostate cancer. Tissue microarrays from 535 patients were constructed from viable and representative tumor epithelial and stromal areas of primary PC tumors, as well as from normal epithelial and stromal areas. Immunohistochemistry was used to evaluate the density of CD3+, CD4+, CD8+, and CD20+ lymphocytes in both tumor epithelial and tumor stromal areas. In univariate analysis, a high density of CD3+ (P = 0.037) and CD8+ lymphocytes (P = 0.010) in tumor epithelial areas was associated with significantly shorter biochemical failure-free survival. When analyzing both tumor epithelial and stromal tissue compartments as one entity, similar relationships were observed for CD3+ (P = 0.046), CD4+ (P = 0.026), and CD8+ (P = 0.003) lymphocytes. In multivariate analysis, high densities of CD8+ lymphocytes limited to tumor epithelial areas (HR = 1.45, P = 0.032), as well as in the total tumor tissue (HR = 1.57, P = 0.007), were independent negative prognostic factors for biochemical failure-free survival. A high density of CD8+ lymphocytes, especially in tumor epithelial areas, is an independent negative prognostic factor for biochemical failure-free survival.

Tumor Genetic Analyses of Patients with Metastatic Renal Cell Carcinoma and Extended Benefit from mTOR Inhibitor Therapy

Rapalogs are allosteric mTOR inhibitors and approved agents for advanced kidney cancer. Reports of clonal heterogeneity in this disease challenge the concept of targeted monotherapy, yet a small subset of patients derives extended benefit. Our aim was to analyze such outliers and explore the genomic background of extreme rapalog sensitivity in the context of intratumor heterogeneity. We analyzed archived tumor tissue of 5 patients with renal cell carcinoma, who previously achieved durable disease control with rapalogs (median duration, 28 months). DNA was extracted from spatially separate areas of primary tumors and metastases. Custom target capture and ultradeep sequencing was used to identify alterations across 230 target genes. Whole-exome sequence analysis was added to investigate genes beyond this original target list. Five long-term responders contributed 14 specimens to explore clonal heterogeneity. Genomic alterations with activating effect on mTOR signaling were detected in 11 of 14 specimens, offering plausible explanation for exceptional treatment response through alterations in two genes (TSC1 and MTOR). In two subjects, distinct yet functionally convergent alterations activated the mTOR pathway in spatially separate sites. In 1 patient, concurrent genomic events occurred in two separate pathway components across different tumor regions. Analysis of outlier cases can facilitate identification of potential biomarkers for targeted agents, and we implicate two genes as candidates for further study in this class of drugs. The previously reported phenomenon of clonal convergence can occur within a targetable pathway which might have implications for biomarker development beyond this disease and this class of agents.

An unusual anatomic and geographic location of primary germinoma of the fourth ventricle

Intracranial germinoma is most commonly found in the pineal and suprasellar regions. The medulla oblongata and fourth ventricle are rare sites of primary germinoma, with only 12 previous patients reported, all from the Far East. To our knowledge, we report the first patient from Europe. A 25-year-old female of Afro-Caribbean origin presented with several weeks of worsening migraines, dizziness, tachycardia and veering to the right whilst walking. MRI revealed a lesion in the fourth ventricle, which was treated with surgical debulking and post operative radiotherapy. Two months following completion of radiotherapy, MRI showed almost complete resolution of the enhancing disease within the primary tumour area and no intraspinal pathological enhancement. This patient highlights the importance of considering germinoma in the differential diagnosis of all medullary masses with extension into the fourth ventricle irrespective of geographic location.

Use of quantitative diffusion-weighted magnetic resonance imaging to predict human papilloma virus status in patients with oropharyngeal squamous cell carcinoma

Although identification of human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no imaging modality can currently determine whether a tumor is HPV-related. In this retrospective study, 26 patients with OPSCC confined to the lateral wall or the base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a region of interest covering the largest available primary tumor area of OPSCC on a single slice of the ADC map were calculated using two b values (0 and 1,000 s/mm(2)). Mean and minimum ADCs were compared with HPV status, using p16 immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum ADCs for HPV(+) OPSCC were significantly lower than those for HPV(-) OPSCC. A cut-off value of mean ADC for HPV(+) OPSCC of 1.027 × 10(-3) mm(2)/s yielded sensitivity and specificity of 83.33 and 78.57%, respectively. In conclusion, the present study indicates that ADC could be used to predict HPV status in patients with OPSCC.

Syk is low-expressed in non-small-cell lung cancer and inversely correlates with patient's survival

The protein tyrosine kinases (PTKs) are a group of enzyme proteins that can phosphorylate substrate protein tyrosine residues, and are involved in many signal transduction pathways. They also play an important role in the control of cell differentiation, proliferation, and spreading. A recent study has found that Syk, as a tumor suppressor of PTKs, is closely related to tumor invasion and metastasis [1]. Syk has been also showed to have potential inhibitory effect in breast, gastric, and pancreatic cancers [2–4]. Sung et al. [5] found that in the mouse mammary gland, loss of one Syk allele profoundly increased proliferation, ductal branching, and invasion of epithelial cells through the mammary fat pad during puberty, and that mammary carcinoma developed after 1 year. An increasing number of clinical studies have revealed a correlation between reduced Syk expression and increased risk of metastasis formation, and Syk is assigned as a potential new prognostic marker in different tumor types [6]. In this study, we examined the expression of Syk in non-small-cell lung cancer (NSCLC) and analyzed its association with the prognosis. The study approved by the Ethics Committee of the Second Hospital of Shandong University included 70 patients (54 males, 16 females; median age of 61 years, ranged from 41 to 76 years) with NSCLC that were diagnosed in the Department of Thoracic Surgery, the Second Hospital of Shandong University. In 70 cases, 28 were diagnosed as adenocarcinoma, 36 squamous-cell carcinoma and 6 large-cell carcinoma. According to Primary Lung Cancer Diagnostic and Treatment Practices (2001), 13 cases belonged to stage I, 33 stage II, 19 stage III, and 5 stage IV. None of the patients received radiation or chemotherapy before surgery. All patients were followed up from January 2007 to December 2010. Tumor tissues were taken from primary tumor area, avoiding necrosis and inflammatory areas. Adjacent tissues were from 2 cm next to the tumor material, and normal lung tissues from 5 cm next to tumor margin. Pathological examination showed no carcinoma cells. Syk expression was immunohistochemically examined using mouse anti-human Syk monoclonal antibody (NeoMarkerS, Fremont, USA) under a light microscope. Three fields of cells were counted, respectively at 400 magnification to determine whether the cells were positive for Syk, and the percentage of stained cells was averaged. Specimens were regarded as Syk negative if ,5% of the cells were stained, 5%–25% as ‘þ’, 25%– 50% as ‘þþ’, and .50% as ‘þþþ’ according to many previous reports [7,8]. The results showed that brown particles could be seen in the cytoplasm in Syk-positive cells under a light microscope (Fig. 1). Syk expression rates were 5.7%, 95.7%, and 100% in tumor, adjacent lung cells, and normal lung cells, respectively. The positive rates were 5.6% in squamous-cell carcinoma, 3.6% in adenocarcinoma, and 16.7% in largecell carcinoma (P 1⁄4 0.394). Syk expression rate in NSCLC tumor cells was significantly lower compared with those in normal lung tissue and adjacent lung tissue (P, 0.05), while there was no difference between adjacent lung tissue and normal lung tissue. These results are similar to previous reports about Syk expression in other types of malignant tumors [4]. However, unlike those reported in previous studies, the Syk expression rates among patients of different pathologic types, differentiation, and clinical stages did not reveal any statistically significant differences. A previous study showed [6] that Syk expression was negatively correlated with differentiation and clinical stages of malignant tumors such as pancreatic cancer, esophageal squamous cell carcinoma, and endometrial cancer. We also noticed that the positive rate of Syk expression in our study was much lower than those reported in previous literatures. This may be explained by the following factors: very low expression of Syk in NSCLC, small sample size, and experimental techniques. Large sample volume and other experimental methods are needed for further study. Other associations between Syk expression and lymph node metastasis, tumor size, and tumor node metastasis have been reported [9], and the results also need further validation. In our study, 47 patients survived .3 years, and Syk expression in this group (8.57%) was higher than that with Acta Biochim Biophys Sin 2013, 45: 149–151 | a The Author 2012. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. DOI: 10.1093/abbs/gms102. Advance Access Publication 2 December 2012

Sunlight may increase the FDG uptake value in primary tumors of patients with non-small cell lung cancer

Currently, positron emission tomography with computerized tomography (PET-CT) is the most sensitive technique for detecting extracranial metastases in non-small cell lung cancer (NSCLC). It has been reported that there is a correlation between the maximal standardized uptake value (SUVmax) of primary tumors and prognosis in patients with NSCLC. The effect of sunlight exposure on PET-CT SUVmax value is not known. Therefore, we aimed to evaluate the effect of sunlight exposure on PET-CT SUVmax value in patients with NSCLC. A total of 290 patients with NSCLC from two different regions of Turkey (Kayseri, n=168 and Adana, n=122) that have different climate and sunlight exposure intensity, were included in the study. Age, gender, histology of cancer, cancer stage, smoking status, comorbidity and SUVmax of the primary tumor area at the time of staging were evaluated as prognostic factors. In the multivariate analysis, we detected that the region was the only independent factor affecting SUVmax (P=0.019). We identified that warmer climate and more sunlight exposure significantly increases the SUVmax value of the primary tumor area in patients with NSCLC. Further studies are warranted to clarify the issue.

Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer

BackgroundThe immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.MethodsOn immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.ResultsThe expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.ConclusionsStromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer.

Endostatin neoadjuvant gene therapy extends survival in an orthotopic metastatic mouse model of renal cell carcinoma

Despite recent advances in targeted therapy, renal cell carcinoma (RCC) remains one of the most lethal urologic malignancies. Approximately 30% of patients with localised RCC will develop metastases after curative surgery. Presurgical therapy has been explored for treatment of localised RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential use of an antiangiogenic agent as a neoadjuvant therapy in an orthotopic metastatic mouse model of RCC. BALB/c mice bearing Renca cells were treated before nephrectomy with NIH/3T3-LendSN cells. At the end of the experiment, ES serum levels were measured. Primary and metastatic tumour area and microvascular area were determined. In the survival studies, mice were monitored daily until they died. ES serum levels in treated mice were higher in the control group (P<0.05). The median primary tumour area and the mean microvascular area were significantly lower in the ES-treated group compared to control group (P<0.05). The proliferation of Renca cells in the ES-treated group was significantly reduced compared with the control group (P<0.01). ES therapy led to a significant reduction in the number of pulmonary metastatic nodules compared with the control group (P<0.01). Kaplan–Meier survival curves showed that the probability of survival was significantly higher in mice receiving ES therapy (P=0.0243, Log-Rank test). Our results indicated that neoadjuvant ES gene therapy has the potential to decrease tumour burden, extend survival, and may have clinical benefit in the management of RCC.

The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols

BackgroundLocal recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. Patients and methodsWe analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. ResultsMedian follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. ConclusionsPatient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.

Diagnóstico Precoce, Tratamento Conservador e Remissão Completa de Osteorradionecrose de Mandíbula - Relato de Caso

IntroductionOsteoradionecrosis (ORN) is characterized as one of radiotherapy's late adverse effects which causes great suffering and compromises patient's quality of life. The classical treatments for ORN are the hyperbaric therapy and surgery (mandibulectomy), quite expensive procedures with controversial indication. Conversely, the effectiveness of conservative treatments, such as topical chlorhexidine mouthwashes, is not well established in the literature. ObjectiveTo report the clinical case and the results in the conservative treatment and control protocols of the ORN in mandible established in a public health service. Case reporta black 45-year-old female patient was treated for squamous cell carcinoma in the past 3 years. She underwent partial glossectomy and adjuvant radiotherapy (7500Cg) on primary tumor area and neck. Patient was referred with a painful condition exhibiting multiple areas of bone exposure of about 2.5cm in its longest axis. Three-times a day mouthwashes with aqueous chlorhexidine gluconate solution 0.12% was prescribed for an indefinite period associated with rigorous oral hygiene and elimination possible oral irritants. Clinical follow was performed weekly until early response and monthly after this period. Two weeks after initial treatment there was complete remission of prodromal symptoms, and after six months sequestrectomy treatment was indicated under antibiotic prophylaxis. Total mucosa covered the bone defect 4 weeks after surgery. Discussion and ConclusionThe treatment was effective. The institution of conservative therapy avoided the necessity of hyperbaric therapy or surgical resection block (mandibulectomy). The results offered less morbidity to the patient and rationalization of the public health resources.

Utility of response evaluation to neo-adjuvant chemotherapy by 18F-fluorodeoxyglucose-positron emission tomography in locally advanced esophageal squamous cell carcinoma

Neoadjuvant chemotherapy (NACT) has been frequently used for locally advanced esophageal squamous cell cancer (ESCC). It is therefore important to establish criteria for evaluating the response to NACT based on survival analysis. This study analyzed 100 patients with ESCC (cT1, 2/3/4:25/57/18, cN0/1/M1lym: 5/59/36) who received NACT (5-fluorouracil, adriamycin, and cisplatin) followed by surgical resection. NACT response was monitored using (18)F-fluorodeoxyglucose-positron emission tomography (PET) and computed tomography by measuring pre- and post-NACT maximal standardized uptake value (SUVmax) and area of primary tumor, respectively. The associations between NACT and clinicopathological factors including prognosis were analyzed. The mean ± SEM values of pre- and post-NACT SUVmax were 12.23 ± 4.62 and 6.31 ± 5.41, respectively, and the mean/median SUVmax reduction was 59.50%/73.45%. The most significant difference in survival between responders and non-responders was at 70% of cutoff value based on every 10% stepwise cutoff analysis (2-year progression-free survival [PFS]: 57.7% vs 25.1%; hazard ratio [HR] = 2.864; P = .0004). Univariate analysis indicated a correlation between PFS and number of cN before NACT, SUVmax reduction, decrease in tumor area, pT, and number of pN, while cT before NACT and pathological response to NACT showed no association. Multivariate analysis identified number of cN before NACT (HR = 2.537; P = .0092), SUVmax reduction (HR = 3.202; P = .0072), and number of pN (HR = 2.226; P = .0146) as independent prognostic predictors. By determining the optimal cutoff value based on survival analysis, we evaluated patient responses to NACT using PET. Such evaluation could be valuable in formulating treatment strategies for ESCC.

A prospective comparision of sequential chemoradiation vs concurrent chemoradiation in locally advanced oropharyngeal carcinomas

Purpose: Induction chemotherapy has shown to provide consistent benefit for local control in primary treatment of advanced oropharyngeal cancer. The beneficial role of chemoradiation following induction chemotherapy over concurrent chemoradiation has not been evaluated. Present study evaluates the same prospectively. Method: Out of 135 patients of locally advanced oropharyngeal carcinoma, 105 patients were found eligible and randomized to treat either with induction chemotherapy consisting of 2-3 cycles of cisplatin and 5- Florouracil followed by low dose weekly cisplatin based chemoradiotherapy (treatment arm: n=48) or chemoradiotherapy only (control arm: n=57). The primary tumor and regional lymph drainage areas received 66-70 Gy in 6.5 to 7 weeks by fractionated dose schedule. Results: The response rate and acute toxicity (primary end points) in both the arms were found to be similar (P>0.05) The points disease free survival and overall survival (secondary end points) were significantly (P

Residual specimen cellularity after neoadjuvant chemotherapy for breast cancer

Neoadjuvant chemotherapy for breast cancer reduces tumour cellularity, the percentage of the primary tumour area that is composed of invasive tumour cells. Minimal residual tumour cellularity (5 per cent or less of tumour area composed of invasive tumour cells) may be associated with an increased risk of false-negative intraoperative margins. The aim of this study was to evaluate the incidence of minimal residual tumour cellularity after neoadjuvant chemotherapy and its impact on the frequency of false-negative margins and conversion from breast-conserving surgery to mastectomy. The final pathology slides of 510 patients who had surgery after neoadjuvant chemotherapy were reviewed. Of 396 patients with residual invasive breast cancer after neoadjuvant chemotherapy, 100 specimens (25.3 per cent) had minimal residual cellularity; this was more frequent in patients with invasive lobular carcinoma (17.0 versus 5.1 per cent; P < 0.001) or well and moderately differentiated carcinoma (68.0 versus 52.4 per cent; P = 0.007). Among 149 patients who had initial breast-conserving surgery, false-negative intraoperative margin rates were 23 per cent in specimens with minimal and 13.8 per cent in those with higher residual cellularity (P = 0.210). There was no significant difference in the rate of conversion to mastectomy between the groups. Minimal residual cellularity after neoadjuvant chemotherapy occurred in about 25 per cent of specimens, but did not alter the rate of false-negative intraoperative margins.

Probleme der Residualtumorklassifikation – speziell R1

The completeness of tumor removal is described in the residual tumor classification. Residual tumor may be found in the area of primary tumor and its regional lymph nodes and/or at distant sites. The R classification reflects the effects of treatment and influences further treatment planning. Therefore very careful use is necessary, including thorough pathohistological examination of resection margins to ascertain an R0 resection or to prove an R1 situation.

Immunohistochemical assessment of fibronectin and tenascin and their integrin receptors α5 β1 and α9 β1 in gastric and colorectal cancers with lymph node and liver metastases

The aim of the current study was to assess immunohistochemically and compare the level of expression of tenascin (TN) and fibronectin (FN) and their integrin receptors alpha9beta1 and alpha5beta1 in the primary colorectal and gastric tumors, and in corresponding lymph node and liver metastases from 53 patients. We detected similar high deposition of the studied ECM proteins and their receptors in the stroma of primary tumors and in liver metastases and a lower deposition in lymph node metastases. Cytoplasmic immune reaction for FN and TN was also seen in the tumor cells. A pronounced co-localization of immune deposits for FN and TN and their receptors was found in the stroma of the center and the invasion front (IF) (p<0.0001). A significant decrease of FN immune signal was observed in the IF in primary tumors and liver metastases (p<0.0001). The levels of immunolabeling of FN and TN correlated with the differentiation grade of primary tumors (p<0.0001). In conclusion, we may say that there is heterogeneous deposition of TN, FN and their integrin receptors in the different areas of primary colorectal and gastric tumors and of their metastases. These findings imply that the studied proteins may be involved in cell processes such as growth, adhesion, migration and apoptosis.