Lymphovascular Emboli Research Articles

Indian Council of Medical Research consensus document for the management of tongue cancer.

EXECUTIVE SUMMARY The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Early diagnosis is imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site).Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck.Early stage cancers (stage I & II) require single modality treatment – either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features [lymphovascular emboli (LVE), perineural invasion (PNI), poorly differentiated, node +, close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease.Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above.Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage.Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms.Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2nd year follow up is done at 4-6 months interval. At each follow up screening for local/regional recurrence and second primary is done. Imaging is done only when indicated.

Pathologic characteristics of pancreatic cancer in Shanghai urban area:preliminary analysis of 350 cases

Objective:To investigate the pathologic characteristics and differential diagnosis of pancreatic cancer among residents in Shanghai urban area.Methods:A population-based large case-control study was performed in patients with pancreatic cancer between December 2006 and January 2011 in Shanghai urban area.The pathologic slides from 387 cases of pancreatic cancer were collected and reviewed by five experienced pathologists.The pathologic diagnosis was determined according to WHO Classification of Tumors of the Digestive System,Fourth Edition(2010).Results:Three hundred and fifty cases(90.4%) were confirmed as pancreatic cancer.Most of the pathologic slides were obtained from resected tissues of pancreatic cancer(311/350,88.9%).The average diameter of the tumor was 4 cm,and 56.6%(n = 198) of the tumors were located in the head of pancreas.The ductal adenocarcinoma was the most common histologic subtype(n = 311,89.0%),followed by pancreatic neuroendocrine tumors(n = 15,4.3%).The most common histologic grades were Ⅱ/Ⅲ(n = 252).According to TNM staging system,40 cases had stage ⅠA,209 cases had stages ⅠB/ⅡA,and 80 cases had stage ⅡB.The perineural invasion was identified in 175 cases,and the lymphovascular and/or venous emboli were identified in 56 cases.Only one case was misdiagnosed.Conclusion:The understanding of pathology of pancreatic cancer in Shanghai urban area was improved through this pathologic review.

Prevalence of molecular subtypes of invasive breast cancer: A retrospective study

BackgroundClassification of breast cancers into different molecular subtypes using immunohistochemistry as a surrogate tool to DNA microarray technology has been identified. Aim of this study was to find the precise prevalence of molecular subtypes of invasive breast carcinoma using immunohistochemistry and to correlate it with histological and clinical prognostic factors. MethodsA descriptive study design wherein 56 breast carcinoma cases diagnosed between May 2012 and Apr 2014 were reviewed and molecular subtyped using relevant immunohistochemical markers. Age, histological type, tumor size, tumor grade, lymphovascular emboli (LVE), nodal status and basal marker expressions were analyzed for all cases. Correlations between molecular subtypes and clinico-pathological characteristics were evaluated statistically. ResultsIn our study group, average age of patients was 50.5 years and most of patients were diagnosed in stage II (54%). Luminal A subtype was most prevalent 34%, followed by Basal like/Triple negative subtype 25%. Luminal B and Her2/neu subtypes had same prevalence i.e. 18% each and Breast Tissue like/Unclassified subtype/Penta Negative subtype was 5%. All cases demonstrated positivity for the luminal cytokeratins 8/18. Histological grade and ER negative status showed strong correlations with basal markers. ConclusionOn the basis of hormone receptor, Her2 neu, EGFR and CK 5/6 expressions, breast carcinoma cases were classified into five distinct molecular subtypes which show significant differences in regards to morphological features, prognostic markers and there by predicting possible clinical outcome.

Breast Cancer in Women of Younger than 35 Years: A Single Center Study

Aim: Breast cancer in women younger than 35 years old is uncommon and only accounts for 2% of all breast cancers diagnosed in Western countries. However, there is paucity of data on breast cancer in women younger than 35 years old in India. The aim of this study was to assess clinicopathological parameters in these young breast cancer patients. Methods: This retrospective study summarized data on women younger than 35 years with breast cancer between August 2012 and July 2013 from tertiary cancer center in India. Results: Out of a total of 320 patients, 36 were younger than 35 years old in this period of time and the median age was 32 years. A breast lump was the most commonly presented symptom with an average symptom duration of four months. The median age of the first childbirth was 22 years. Most of the patients had a stage III disease (52%) followed by stage II (33%). All patients had invasive ductal carcinoma and 86% of patients had high-grade tumors. 51% of patients were lymphnode-positive, and lympho vascular emboli were present in 43% of cases. Estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) positivity occurred in 38.9% and 22.2% of patients, respectively and 50% of patients were triple negative. Conclusion: Breast cancer occurring in women younger than 35 years old constituted 11.3% of all breast cancer cases in Kidwai Memorial Institute of Oncology, India. They had high tumor grade with a larger size and an increased incidence of lympho vascular emboli, which lead to aggressive behaviors and poor prognosis. This study suggest that early onset of breast cancer must be considered as a diagnostic possibility in Indian patients presenting palpable masses in the mammary glands.

Oncological and functional results after the surgical treatment of parotid cancer

The objective of this study was to analyze the oncological and functional outcomes after the surgical treatment of parotid cancer. We reviewed 80 primary parotid carcinomas retrospectively. A superficial parotidectomy was performed in 10 patients; 27 patients underwent total parotidectomy and 43 patients underwent radical parotidectomy. A facial–facial nerve anastomosis was chosen for the facial nerve reconstruction in eight patients, while an interpositional graft was selected in 24 patients. The overall N-positive rate of pathology was 21.3%. The rate of occult metastasis was 8.1%. High-grade carcinoma and lymphovascular emboli were independent factors for nodal metastasis. The 5-year disease-free survival and overall survival rates were 79.7% and 78.8%, respectively. Preoperative facial nerve palsy and extraparenchymal invasion were the independent factors associated with poor disease-free survival. Of the 41 patients in the facial nerve preservation group, 13 (31.7%) had transient facial nerve paresis. In the facial nerve sacrifice group of 39 cases, (sub)total recovery (House–Brackmann grade I/II) occurred in 14 (35.9%), partial recovery (House–Brackmann grade III/IV) in 13 (33.3%), and no recovery (House–Brackmann grade V) in 12 (30.8%). Facial nerve palsy upon presentation and extraparenchymal invasion indicate a grave prognosis. Facial nerve function after proper reconstruction is tolerable.

Abstract A01: Pharmacological approaches to metastatic disease using an Inflammatory Breast Cancer model

Abstract Goal of Study: The lymphovascular embolus is a marker of breast cancer aggressiveness, recurrence, metastatic progression and therapeutic failure. This is especially reflective in inflammatory breast cancer (IBC) which presents as florid intravasation in situ of the lymphovasculature by tumor emboli. This study utilizes a novel 3-dimensional (3D) in vitro and in vivo model of IBC to systematically and strategically develop pharmacological approaches in the treatment of both IBC and metastatic disease. Background: Intravasation, the rate-limiting step of metastasis, is extremely important in tumor progression and expansion, yet the mechanism underlying intravasation is still poorly understood. The consequence of intravasation is the resultant lymphovascular embolus – the key defining feature of metastasis. This is most prevalent in IBC, the most lethal form of breast cancer. Clinical IBC features, erythema, peau d'orange (dimpling of thickened skin) and warmth are due to the IBC signature phenotype, namely extensive intravasation in situ of the lymphatic and blood vessels by tumor emboli. Nearly 100% of all women with IBC have lymph node involvement and approximately 25% of patients with IBC have distant metastases at diagnosis. The IBC xenograft model, MARY-X, has precisely captured the IBC phenotype, where the tumor emboli grow exclusively within the murine lymphatic and blood vessels and exhibit erythema of the overlying skin. MARY-X is an invaluable preclinical IBC model and an overall model of metastasis providing a means to validate and translate therapeutic strategies. MARY-X, in vitro, is a cellular derivative of primary tumor explants. These tumor cells form tight, compact aggregates of cells termed “MARY-X spheroids”. Comparable to human IBC emboli, a persistent, over-expression of an intact E-cadherin/α, β-catenin axis mediates the compaction of both in vitro and in vivo MARY-X spheroids and tumor emboli, respectively. These comparative architectural features (i.e. mimics the in vivo metastasis) of the spheroid of MARY-X provide an in vitro model with tractable in vivo applications. Research Strategy: By exploiting the MARY-X in vitro 3-D model, high throughput (HTP) screening is performed to systematically probe the factors involved in maintenance of tumor emboli architecture as it pertains to sensitivity/resistance to therapeutics in an overall effort to develop efficacious therapeutics for treatment of IBC and metastatic disease. Additionally, MARY-X spheroids co-cultured with bone marrow derived cells (BMDCs) in matrigel overlays are employed to assess targeting of mediators of crosstalk between tumor spheroid/embolus soluble factors (e.g. cytokines, exosomes) and the microenvironment. Soluble factors identified as mediators (i.e. targets) of metastatic progression, that showed the most promise in the HTP screen, are further validated in the in vivo preclinical model, MARY-X. A significant decrease in vessel density of the MARY-X tumor will be indicative of successful blocking of this ‘crosstalk’ i.e. lymphovasculogenesis or the formation of lymphovascular emboli (i.e. intravasation) – the defining feature of metastatic disease. Preliminary Data and Conclusions: Preliminary data show that dissolution of the spheroid/embolus augment apoptotic effects of chemo/irradiation therapy. Suggesting that apoptosis resistance of lymphovascular emboli may be independent of traditional apoptotic mechanisms. Therefore, therapy evasion, in part, is due to formation and maintenance of the architectural features of the lymphovascular embolus. In addition, abrogation of ‘crosstalk’ has proven to hinder the establishment of lymphovascular emboli. Citation Format: Mary L. Alpaugh, Emmanuel Theodorakis. Pharmacological approaches to metastatic disease using an Inflammatory Breast Cancer model. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A01.

Indian Council of Medical Research consensus document for the management of colorectal cancer.

The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Early diagnosis is imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site).Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck.Early stage cancers (stage I & II) require single modality treatment - either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features [lymphovascular emboli (LVE), perineural invasion (PNI), poorly differentiated, node +, close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease.Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above.Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage.Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms.Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2(nd) year follow up is done at 4-6 months interval. At each follow up screening for local/regional recurrence and second primary is done. Imaging is done only when indicated.

Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India.

The proportion of breast cancer is rising in India. It presents at a younger age in India as compared to the western countries. This is a retrospective study of 86 breast cancer patients less than 40 years treated in a single center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome. Data were collected from medical records. Variables such as age, stage, surgery, chemotherapy, tumor size, grade, nodal status, perinodal extension, lymphovascular emboli, estrogen receptor, progesterone receptor, and HER-2 neu were analyzed in relation to outcome. Out of total 613 breast cancer patients, 91 (14.8%) were younger than 40 years. Five were excluded due to incomplete data; hence, 86 patients were included in this study. Median tumor size was 3 cm and lymph node positivity was 56.9%. Lymphovascular emboli were positive in 48.8% and perinodal extension was positive in 41.8%. Estrogen receptor positivity was 34.8%, progesterone receptor positivity was 45.3%, and triple negativity was 45.3%. The median follow-up period was 27 months with disease free survival being 73.2% and overall survival being 87.2%. In univariate analysis, the factors significantly associated with survival were stage at presentation, presence of lymphovascular emboli, perinodal extension and grade of the tumor. In multivariate analysis grade of tumor was the only significant factor. In young women with breast cancer, the factors significantly associated with survival were clinical stage at presentation, the presence of lymphovascular emboli and perinodal extension and grade of tumor.

Clinical and prognostic significance of EGFR, MMP-13 and E-cadherin expressions in colorectal signet ring cell adenocarcinoma

Colorectal signet ring cell adenocarcinoma (SRA) is a rare entity that accounts for 1% of colorectal carcinoma (CRC). SRA has specific clinicopathological features different from ordinary adenocarcinoma (OA) and colloid carcinoma (CC). In this study, we aimed to compare SRA, OA and CC regarding clinicopathological, histological parameters, survival, EGFR, MMP-13 and E-cadherin expressions. We studied tumor tissue specimens from 19 patients with SRA, 47 patients with OA and 56 patients with CC. High density manual tissue microarrays were constructed. SRA was significantly associated with younger age, more lymph node metastasis, advanced stage, more lymphovascular emboli, perineural invasion and worse disease-free and overall survival. OA was significantly associated with more peritumoral lymphocytic infiltrate and microscopic abscess formation than SRA. SRA expressed EGFR, MMP-13 and E-cadherin in significantly lower rates than OA. The same was true for CC but with no significant difference of MMP-13 expression with SRA. Neither EGFR, MMP-13 nor E-cadherin expression showed a significant impact on disease-free or overall survival in patients with SRA. Our results support that targeted therapies against EGFR, MMP-13 and E-cadherin are not expected to be useful in patients with SRA. Further molecular studies are needed to introduce tailored targeted therapies for SRA.

Unveiling lymph node metastasis in early gastric cancer.

With respect to gastric cancer treatment, improvements in endoscopic techniques and novel therapeutic modalities [such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD)] have been developed. Currently, EMR/ESD procedures are widely accepted treatment modalities for early gastric cancer (EGC). These procedures are most widely accepted in Asia, including in Korea and Japan. In the present era of endoscopic resection, accurate prediction of lymph node (LN) metastasis is a critical component of selecting suitable patients for EMR/ESD. Generally, indications for EMR/ESD are based on large Japanese datasets, which indicate that there is almost no risk of LN metastasis in the subgroup of EGC cases. However, there is some controversy among investigators regarding the validity of these criteria. Further, there are currently no accurate methods to predict LN metastasis in gastric cancer (for example, radiologic methods or methods based on molecular biomarkers). We recommend the use of a 2-step method for the management of early gastric cancer using endoscopic resection. The first step is the selection of suitable patients for endoscopic resection, based on endoscopic and histopathologic findings. After endoscopic resection, additional surgical intervention could be determined on the basis of a comprehensive review of the endoscopic mucosal resection/endoscopic submucosal dissection specimen, including lymphovascular tumor emboli, tumor size, histologic type, and depth of invasion. However, evaluation of clinical application data is essential for validating this recommendation. Moreover, gastroenterologists, surgeons, and pathologists should closely collaborate and communicate during these decision-making processes.

Étude clinique et histopronostique de 50 cas de porocarcinome eccrine

Eccrine porocarcinoma is a rare cutaneous tumor arising from the intra-epidermal portion of eccrine sweat glands, the acrosyringium. Histoprognostic studies in large series are rare. Herein, we report a retrospective study of 50 cases. Fifty cases of porocarcinoma were retrieved from a histopathological register. Each histopathological sample was evaluated for the following criteria: presence or absence of dermal invasion, pattern of the infiltrative component (pushing or infiltrative), tumor thickness, lymphovascular emboli, perineural invasion and mitotic index. Clinical data and outcome were also retrieved for each patient. Mean patient age was 77 years (range: 43-99 years). The mean duration of progression prior to diagnosis was 4 years and 5 months. The 2 most common skin locations were the head (38%) and lower limbs (20%). The lesions showed no specific distinctive clinical features. Six cases were in situ, and 44 were invasive (23 with limited infiltration and 20 with scattered infiltration). Mean tumor thickness was 4.37 mm (range: 0.5 to 20 mm). Neighboring or remote epidermal involvement was noted in 7 cases. Lymphovascular emboli were observed in 3 cases. No cases of neurotropism were observed. The average mitotic index was 6.5 mitoses/high power (×400) field. A mean follow-up of 24.3 months was available for 48 patients. Local recurrence was noted in 5 patients, 4 of whom died from visceral metastases. These 5 cases showed no distinctive clinical features, a scattered pattern of the invasive component, cuticular cells, significant tumor thickness (mean 12.8 mm, range 9-20 mm), and an elevated mitotic index. Two histopathological criteria were significantly associated with a metastatic outcome: scattered pattern of the dermal invasive component (P=0.04) and significant tumor thickness, above 10mm (P<0.01). Porocarcinoma is a tumor without any particular clinical criteria to distinguish it from squamous cell carcinoma. The architecture of the invasive component and tumor thickness constitute 2 important histoprognostic criteria.

Lymph node metastasis in early gastric cancer: evaluation of a novel method for measuring submucosal invasion and development of a nodal predicting index

After endoscopic resection of early gastric cancer (EGC), it is imperative to accurately determine whether follow-up surgery is indicated, since this technique is used as a first line of treatment. Herein, we developed a scoring system to indicate the risk of lymph node metastasis in submucosal EGC (smEGC), and present a novel method to measure depth of submucosal invasion. In our series, 15.9% of the smEGC presented with lymph node metastasis. A nodal prediction index, based on the variables extracted from the univariate analysis and defined as nodal prediction index = (2.128 × lymphovascular tumor emboli) + (1.083 × submucosal invasion width ≥ 0.75 cm) + (0.507 × submucosal invasion depth ≥ 1000 μm) + (0.515 × infiltrative growth pattern), yielded an area under the receiver operating characteristic curve of 0.809 (P =.000, 95% CI = 0.713-0.096) in a training group, and showed comparable result in validation group (0.886, P =.000, 95% CI = 0.796-0.977). Depth of invasion was statistically higher in the metastatic group when measured from the lowest point of an imaginary line in continuity with the adjacent muscularis mucosa to the point of deepest tumor penetration, but not when using the classic measurement method. The area under the receiver operating characteristic curve of the alternative measurement method was 0.652 (P =.013, 95% CI = 0.550-0.754) compared to 0.620 for the classic measurement method (P =.0480, 95% CI = 0.509-0.731). In deciding whether surgery is indicated after endoscopic submucosal dissection for smEGCs, we recommend to test our alternative method of measuring submucosal invasion and to evaluate our nodal prediction index as an adjunct tool.

Relationship between colorectal adenocarcinoma with invasive micropapillary carcinoma component and lymph node metastasis

To investigate the relationship between colorectal adenocarcinoma with invasive micropapillary carcinoma (IMPC) component, lymphovascular invasion, and lymph node metastasis. One hundred and thirty one cases of colorectal adenocarcinoma with invasive micropapillary carcinoma component were evaluated by H&E and immunohistochemical staining. The main pathological features, percentage of IMPC component, lymphovascular invasion, and lymph node metastasis were assessed and compared to 296 cases of conventional colorectal adenocarcinoma. The maximum diameter of the tumors of the IMPC group was significantly lower than the conventional group. The degree of differentiation, the lymph node metastatic rate, the average number of metastatic lymph nodes, the number of cases with lymphovascular tumor emboli were significantly higher in the IMPC group (P = 0.000). The rate of distant metastasis at operation was higher in the IMPC group (14.5%) compared to the conventional group (10.8%) even though statistical significance was not achieved (P = 0.278) . In IMPC group, as the IMPC component increased, the rate of lymph node metastasis also showed an increasing trend. The rate of lymph node metastasis were 53.0% (157/296) , 67.7% (42/62) and 85.5% (59/69) " respectively" for conventional adenocarcinoma, adenocarcinoma with ≤ 10% IMPC component and adenocarcinoma with > 10% IMPC component; the difference was statistically significant (P = 0.000). Compared to conventional colorectal adenocarcinomas, the colorectal carcinomas with IMPC component show a significantly higher rate of lymphovascular invasion, lymph node metastasis and distant metastasis. The percentage of IMPC component in colorectal adenocarcinoma is significantly correlated to the rate of lymph node metastasis. Therefore, presence of IMPC component and degree of tumor differentiation are predicting factors of lymph node metastasis.

English

Traditionally considered to be a loco-regional disease, head neck cancers metastasize infrequently to distant sites. Among these, skin metastases have been rarely reported and almost always they have been encountered during or after treatment of primary. We present here a case of squamous cell carcinoma of base of tongue with multiple dermal metastases at initial presentation. This report signifies that rarity of such cases must not delay the confirmation of diagnosis since these patients already carry a dismal prognosis. only a month back. Other than a history of heavy smoking for the last 30 years, there were no other forms of addiction. He was neither diabetic, nor hypertensive and had a ECOG performance of '2'. Clinical examination and contrast enhanced CT scan of neck revealed irregular hard mass in base of tongue eroding into left retromolar trigone and hard bilateral neck nodes with the largest one measuring 5.4X 6.2cm.A specimen from the tongue mass showed grade 2(moderately differentiated) squamous cell carcinoma with peri-neural invasion but no lympho-vascular tumor emboli was detected. Punch Biopsy from a skin nodule revealed metastatic squamous cell carcinoma deposits. Metastatic work-up revealed no other sites of metastasis. Routine investigations were essentially normal. The disease was staged to be cT4aN3M1. Salvage chemotherapy with Docetaxel (80mg/m2 on day 1), cisplatin (75mg/m2 on day 1) and 5-Flurouracil (1000mg/m2 day1-4) was initiated within a week and he has tolerated well two such cycles so far. A partial response of the primary and neck nodes has been documented and the skin nodules have completely disappeared (figure 2).

Pathologic definition and number of lymphovascular emboli: impact on lymph node metastasis in endoscopically resected early gastric cancer

Endoscopic submucosal dissection (ESD) is widely accepted as an appropriate treatment modality for early gastric cancer (EGC). Accepted indications for ESD are mostly based on the risk of lymph node (LN) metastasis in EGC. The presence of lymphovascular emboli (LVEs) is the most important risk factor for predicting LN metastasis, but the criteria for diagnosing LVEs are inconsistent and controversial. Here, we defined LVE as the presence of tumor cells within a space according to the following criteria: (1) red cells or lymphocytes surrounding the tumor cells, (2) an endothelial cell lining, and (3) attachment to the vascular wall. We reviewed a series of 102 patients with EGC who underwent gastrectomy after ESD, evaluated the definition of LVE, counted the number of LVEs in ESD specimens, and validated the significance of the definition and number of LVEs with regard to the presence of LN metastasis in gastrectomy specimens using receiver operating characteristic (ROC) curve analysis. Overall, 13 instances (12.7%) of LN metastasis were identified among 102 patients with EGC who underwent gastrectomy after ESD. The LN metastasis-positive group showed higher numbers of definite (4.46 ± 2.45 versus 0.19 ± 0.07), suspicious (3.15 ± 0.76 versus 0.62 ± 0.14), and probable (1.62 ± 0.43 versus 0.43 ± 0.10) LVEs in ESD specimens than the LN metastasis-negative group. In ROC analysis, the area under the ROC curve was 0.851 (95% confidence interval [CI], 0.711-0.991) for definite LVEs, compared with 0.82 (95% CI, 0.698-0.960) for suspicious LVEs and 0.72 (95% CI, 0.549-0.891) for probable LVEs. We recommend the use of strict LVE criteria to predict LN metastasis and determine the need for surgical intervention after ESD.

OP029: Tumor thickness predicts nodal metastases in Gingivobuccal complex cancers

Purpose Cancers of the Gingivobuccal complex (GBC), which comprises of the buccal mucosa, gingivo-buccal sulci and alveolus, are commonly seen in the Indian subcontinent, due to tobacco and betel quid chewing. While tumor thickness is an accepted risk factor for nodal metastases in certain sites of oral cavity, like tongue cancers, its role as a predictor of nodal metastases in GBC cancer is not established. The purpose of this study was: 1. To assess tumor thickness as a predictor of nodal metastases in GBC cancers 2. To find a cut-off value of tumor thickness that would indicate nodal metastases Materials and methods Retrospective analysis of GBC cancers undergoing surgery in our institute from January 2008 to February 2010 was done. Data regarding patient, tumor and nodal factors was documented. Univariate and multivariate analyses were done to find factors predicting nodal metastases. Receiver operated characteristic (ROC) curve was plotted to find cut-off for tumor thickness. Results There were 1058 patients screened, of which 439 were excluded. In 619 eligible patients, 739 neck dissections were performed. Mean tumor thickness was 1.38 cm (range: 0.1–5.5 cm). On univariate analysis, significant predictors of nodal metastases were: gross tumor thickness, primary site, pT stage, and perineural invasion and lymphovascular emboli. On multivariate analysis (logistic regression), tumor thickness was the only significant variable predicting tumor thickness ( p = 0.009). The ROC curve identified 0.45 cm as a reasonable cut off value of tumor thickness that would predict nodal metastases (sensitivity 91%, specificity 86%). Conclusions Gross tumor thickness is a significant determinant of metastatic nodes in GBC cancers. A tumor thickness of 0.45 cm or above in GBC cancers predicts nodal metastases, and this would help guide performing neck dissections in these patients.

Genetic Alterations of K-ras, p53, c-erbB-2, and DPC4 in Pancreatic Ductal Adenocarcinoma and Their Correlation With Patient Survival

The objective of this study was to evaluate genetic alterations of K-ras, p53, c-erbB-2, and deleted in pancreatic cancer, locus 4 (DPC4) genes in pancreatic ductal adenocarcinoma and correlate these changes with patients' overall survival. Between April 2004 and December 2008, 272 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institute. Genetic analyses and immunohistochemical stains were reviewed retrospectively. Alterational rates of each gene were as follows: K-ras, 53.8%; p53, 38.2%; c-erbB-2, 7.3%; DPC4, 81.6%. Subtypes of K-ras gene were as follows: GGT (wild type), 46.2%; GAT, 31.2%; GTT, 14.5%; CGT, 5.6%; TGT, 1.7%; CTG, 0.4%; AGT, 0.4%. K-ras mutation (especially GAT subtype) and DPC4 inactivation resulted in a reduction of postresection survival (P = 0.001 and P = 0.047). Univariate analysis revealed 8 factors affecting to the survival, and multivariate analysis revealed that 6 of them were independently responsible for poor survival of patients: presence of lymphovascular tumor emboli, DPC4 inactivation, poorly differentiated carcinoma, K-ras mutation, presence of lymph node metastasis, and elevated CA-19-9 (>37 U/mL). This study may help to understand the genetic feature of pancreatic cancer and its survival effect in our population. This shows that additional genetic insights would contribute to the improvement of patients' prognosis.

Pathological predictive factors for tumor response in locally advanced breast carcinomas treated with anthracyclin-based neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NACT) is used as a primary treatment for locally advanced breast carcinoma (LABC) and also extended to operable breast cancer. The aim of this study was to evaluate the predictive value of different histological parameters in core biopsy of LABC patients treated with anthracycline-based chemotherapy regimen. Pathological assessment of the excised tumor bed is the gold standard and is essential for identifying the group of patients with pathologic complete response (pCR) or pathologic noncomplete response (pNR). A total of 50 patients with stage II and III breast carcinoma were included in the study. Pretreatment core biopsy histological features include tumor type, histological grade, presence of tumor necrosis, lymphovascular emboli (LVE) and immunohistochemical stains for estrogen receptor (ER) and progesterone receptor (PR) were obtained. Patients were given 3-6 cycles of NACT. Pathological response was assessed. Seven out of 50 patients achieved pCR. A total of 71.4% patients who achieved pCR had tumor necrosis on initial core biopsy while only 30% pNR cases had this feature (P =0.035). Breast carcinoma other than ductal type was chemoresistant. Of 47 core biopsies, LVE was observed in 13 cases (28 %) of which 11 showed axillary node metastasis. None of these 13 cases had pCR, thus having poor predictive value. Pathological parameters like type of tumor, presence of LVE and tumor necrosis in the core biopsy can predict the response to NACT in routine stain. Tumor necrosis and type of breast carcinoma are predictive parameters for tumor responsiveness to NACT. LVE was reliable in predicting axillary lymph node metastasis.

Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes

BackgroundGastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear.MethodsMSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed.ResultsOut of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197).ConclusionsOur data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.

Warty carcinoma of the penis: A clinicopathological study from South India

Aims:There are few studies on the pathology of warty carcinoma (WC) of the penis and these have been from South America. Penile cancers are not uncommon in India. We reviewed the frequency of subtypes of penile squamous carcinoma (SC) and the pathological features and outcome of WC when compared to squamous carcinoma-not otherwise specified (SC-NOS). We also compared the clinicopathological features of WC in our series with those published earlier.Materials and Methods:We studied 103 cases of penile cancers over 6 years. Cases were classified into different subtypes according to established histologic criteria. Clinicopathologic features were studied in detail and compared among the different subtypes, especially between WC and SC-NOS. The patients were followed-up and disease free survival in months was noted.Results:SC-NOS constituted 75.7% of all penile cancer cases in our series. The frequency of other subtypes was WC: 9.7%, verrucous: 3.9%, basaloid type and papillary type: 0.97% each, and mixed types 8.7%. The average tumor size and depth of invasion did not differ significantly between the two subtypes. Frequency of lymphovascular emboli and percentage of lymph node metastasis in WC (30 and 10%) were lesser than in SC-NOS (49.37 and 26.58%), respectively. There were no recurrences after partial penectomy in the WC subtype. In the SC-NOS type, three cases had recurrence after partial/total penectomy.Conclusion:Warty carcinoma constitutes nearly 10% of all penile squamous cell cancers. These patients seem to have a less aggressive behavior than SC-NOS.