Anning Feng

Gastric cardiac carcinomas involving the esophagus are more adequately staged as gastric cancers by the 7th edition of the American Joint Commission on Cancer Staging System

The aim of this study was to compare the 7th with the 6th edition of the American Joint Commission on Cancer Staging System for prognostic stratification of gastric cardiac carcinomas involving the esophagus. We retrospectively compared differences in pathological stages with patient survival between the 7th and the 6th staging systems in 142 consecutive resection cases of this cancer. Patient median age was 65 years. The male–female ratio was 3.3. The epicenter of all tumors was within 5 cm below the gastroesophageal junction. The median tumor size was 5.0 cm. Most tumors (79%) were typical adenocarcinomas and the rest showed uncommon histology types. Using the guidelines for gastric cancer, this group of cancer was better stratified by the 7th than the 6th edition of the staging system, especially for pathological nodal (pN) and overall stage pIIIC. Patients with celiac axis nodal disease had the 5-year survival rate worse than those staged at pN3A and pIIIA. Patients staged at pT3 and pN3B had the 5-year survival rate worse than those at pM1 and pIV. We showed that the overall stage of gastric cardiac carcinomas was better stratified by gastric than by esophageal cancer grouping. We conclude that these tumors are better stratified with the 7th than the 6th edition of the gastric staging system, especially for pIII cancers, and better staged by the new gastric than esophageal cancer staging system. We propose that the staging of these tumors be reverted to gastric grouping and combine pT3 and pN3B into the overall stage pIV.

Comparison of gastro-oesophageal junction carcinomas in Chinese versus American patients.

Huang Q, Fan X, Agoston A T, Feng A, Yu H, Lauwers G, Zhang L & Odze R D 
(2011) Histopathology59, 188–197

Comparison of the 2007 and 2013 ASCO/CAP evaluation systems for HER2 amplification in breast cancer.

It has been proven that chromosome 17 centromere (CEP17) amplification causes misleading human epidermal growth factor receptor 2 (HER2) gene fluorescence in situ hybridization (FISH) results, precluding anti-HER2-based therapy in some patients with breast carcinoma. We used the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) scoring criteria to evaluate HER2 amplification status in 175 cases of breast carcinoma with chromosome 17 polysomy. We used immunohistochemistry (IHC) to determine the HER2 amplification status, and 2-color FISH to detect CEP17, and reviewed the results of initial evaluation using the 2007 ASCO/CAP criteria. Of the 175 cases, 17, 95, and 63 were IHC 0/1+, 2+, and 3+, respectively. Evaluation of IHC HER2 status according to the 2013 ASCO/CAP criteria identified significantly more HER2-positive cases compared to cases evaluated using the 2007 criteria (p<0.05). When the FISH results were evaluated in parallel with the 2013 criteria, we found that 22 cases were not HER2-negative despite the presence of polysomy 17, which, according to the 2013 criteria, indicates HER2-positive status. Our findings indicate that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. In turn, performing FISH and evaluating samples using the 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.

Distal esophageal carcinomas in Chinese patients vary widely in histopathology, but adenocarcinomas remain rare.

In Western countries, distal esophageal adenocarcinoma has outnumbered squamous cell carcinoma because of a dramatic increase in the prevalence of columnar-lined esophagus. Because the relative prevalence of these diseases remains unknown in China, we investigated the histopathology of distal esophageal neoplasm in resection specimens from a high-volume medical center in China. A computerized search of esophageal cancer was conducted in the pathology database between 2004 and 2010. Cancers with epicenter located within 5 cm above the gastroesophageal junction were retained for analysis. Pathology reports were reviewed along with medical, radiologic, and endoscopic records. All histology slides of selected cases were reevaluated (median, 13 per case). Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma were categorized according to the World Health Organization classification of esophageal cancers. The presence of columnar-lined esophagus and other pathologic changes were assessed in cases with residual esophageal mucosa. Among 1101 resections, 204 (19%) qualified for the study. Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma represented 76%, 11%, 3%, 2%, 6%, and 1% of the cases, respectively. Synchronous carcinomas were found in 12% and consisted of primarily squamous cell carcinoma (50%) and proximal gastric adenocarcinoma (38%). Columnar-lined esophagus was detected in 18% of the cases, among which intestinal metaplasia was present in 30% and low-grade dysplasia in 7%. In conclusion, distal esophageal carcinomas in Chinese patients showed a wide histopathologic spectrum with predominant squamous cell carcinoma and rare esophageal adenocarcinoma. Although common, columnar-lined esophagus appears pathogenetically insignificant for most distal esophageal carcinomas.

Pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus

The aim of this study was to systematically investigate clinicopathologic features of the recently described pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus (n = 43). Patient median age was 66 years (range, 51-90 years). The male-to-female ratio was 7.6. Grossly, pancreatic acinar-like adenocarcinoma tumors were nonencapsulated with the median size of 5.5 cm (range, 2-10.5). Bormanns types 1 to 4 tumors were in 7%, 9%, 67%, and 16% cases, respectively. Frank necrosis, hemorrhage, and cysts were rare or absent. Lymphovascular (81%), perineural (74%), and lymph node (81%) invasions were more common in the pancreatic acinar-like adenocarcinoma than in the non-pancreatic acinar-like adenocarcinoma (n = 94) groups. Microscopically, pancreatic acinar-like adenocarcinoma tumors showed acinar (78%), micropapillary (12%), microcystic, solid, trabecular, and mixed neuroendocrine or signet ring (33%) patterns of growth. No adenosquamous differentiation was noted in the pancreatic acinar-like adenocarcinoma group. Nuclei were round to oval with thickened nuclear membrane, stippled chromatin, and single prominent nucleoli. Mitotic figures were variable. The cytoplasm was moderate, eosinophilic, finely granular, and diffusely immunoreactive to the α1-chymotrypsin antibody in all cases to various degrees. Tumor stroma was nondesmoplastic, delicate, and fibrovascular. Pancreatic acinar-like adenocarcinoma tumors staged pI, pII, pIII, and pIV were in 2%, 21%, 70%, and 7% of cases, respectively. The median number of follow-up months after surgery was 29. The 2-year survival rate was 67%, lower than that (73%) in the non-pancreatic acinar-like adenocarcinoma group. A worse overall survival trend was found for patients in the pancreatic acinar-like adenocarcinoma than in non-pancreatic acinar-like adenocarcinoma groups, but the difference was not statistically significant. Age older than 75 years and overall pathology stage were independent risk factors.

Clinicopathological significance of SIRT1 and p300/CBP expression in gastroesophageal junction (GEJ) cancer and the correlation with E-cadherin and MLH1.

SIRT1 and p300/CBP, which are considered to be essential histone deacetylases and acetyltransferases, are also considered to be relative to tumorigenesis because they modulate the expression of several tumor suppressor genes. Therefore, this study investigated the expression of SIRT1 and p300/CBP in gastroesophageal junction (GEJ) cancer and their correlation with E-cadherin and MLH1 in order to explore the clinicopathological significance of SIRT1 and p300/CBP expression and their possible effects involving E-cadherin and MLH1 expression. Tissue microarray technique and immunohistochemical stains were applied to evaluate the SIRT1, p300/CBP, E-cadherin, and MLH1 expression in 176 GEJ cancer tissues and 32 normal GEJ region tissues. The results showed that the over-expression of SIRT1 was associated with a higher number of metastasis lymph nodes, more advanced staging, and shorter mean survival time. SIRT1 and p300/CBP were negatively and positively correlated with the expression of E-cadherin and MLH1, respectively, in the cancer cases. These results indicated a possible effect of SIRT1 and p300/CBP involved in regulating the expression of E-cadherin and MLH1, thus participating in the tumor progression of GEJ cancer.

Gastric mixed adenoneuroendocrine carcinoma: correlation of histologic characteristics with prognosis ☆

Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma (P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification.

Genome profile in a extremely rare case of pulmonary sclerosing pneumocytoma presenting with diffusely-scattered nodules in the right lung

ABSTRACT Background: Pulmonary sclerosing pneumocytoma (PSP) typically presents solitary and peripheral mass, while only rarely cases display unusual multiple lesions. We reported a extremely rare case of PSP with diffusely-scattered nodules in the right lung. Case presentation: Diffusely round-shaped nodular shadows in the right lung were found by CT scan in a 31-year-old Chinese woman. The patient undergone the right pneumnectomy. Grossly, numerous small nodules, up to 2.5 cm in greatest dimension were identified in the upper, middle and lower lobes of the right lung. Histologically, the tumor presented the typical features of PSP, with a variable proportion of solid, sclerotic and papillary patterns. Immunohistochemical staining further revealed that cuboidal surface epithelial cells were positive for TTF-1, EMA, AE1/3 and vimentin (partially), and round or polygonal cells expressed TTF-1, vimentin, EMA (weakly), synaptophysin (partially), progesterone receptor (partially), and estrogen receptor (scatteredly). The patient has been followed up for 83 months after surgery by annual chest CT and no new lesions are detected in her left lung and other organs. The whole-exome sequencing identified 15 somatic mutations genes (MEGF6, DNAH5, AKT1, GPRIN2, PIK3AP1, FBXO40, HERC1, VPS16, MORN1, ZNF474, CTNNB1, ZNF251, TSC1, ATM, KDR). Pathway analysis showed possible pathways like the components of CTNNB1, AKT1, and TSC1 mutations in the PI3K/AKT signalings and AKT1, KDR and ATM in VEGF signaling pathway and AKT1 activation seemed closely related with these pathways. Conclusion: According to our and previous data, PSP with diffuse or multiple lesions is very rare, and the patients are most commonly seen in women in Asian countries. The misdiagnosis rate by clinical and intraoperative frozen-section assessment is high because of the multiple nodules in the lung and its confusing histological features. Long time follow up indicates surgical resection should not be considered as the preferred strategy for treating multiple PSP in the intralobar sites. AKT1 activation may contribute to the development of PSP while the pathogenesis of diffuse or multiple PSP still needs to be further analyzed.

M1921 Gastric Cardiac Cancer Involving the Esophagus Can Be Better Staged by the 7th Than the 6th Edition of AJCC Cancer Staging System

G A A b st ra ct s included patients was 10.21 for CD31 and 11.85 for CD34 in all patients, while VEGF was positive only in 18 patients (45%). The microvessel density was higher in patients with advanced TNM stage, as assessed by both methods (CD31, CD34). Moreover, there was a correlation between the microvessel density and the risk of UGIB (p=0.0436 for CD31 and p=0.0138 for CD34, respectively). VEGF expression was well correlated with TNM stage (especially with the M stage, p<0.0001) and also with the risk of upper GI bleeding (p= 0.0138).Survival rate after first year of follow-up was 37.5% and 30% respectively after two years of follow-up. Survival rate was positively correlated with MVD (reaching statistical significance), while VEGF expression was not correlated with survival rate.Conclusions: According to the results of our study, MVD was involved in local advanced disease, while VEGF was correlated to distant metastasis in gastric cancer patients. There was a clear correlation between VEGF, MVD and the risk of upper GI bleeding. However, the result of our study should be confirmed in future studies with a large number of patients included and preferably multicentric design.