A Rare Case of Persistent Multifocal Cribriform-Morular Thyroid Carcinoma.

Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

GLI1 activation is a key mechanism of erlotinib resistance in human non-small cell lung cancer.

Lung cancer is the leading cause of cancer-associated death worldwide. In recent years, the advancement of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapies has provided clinical benefits for lung cancer patients with EGFR mutations. The response to EGFR-TKI varies in patients with lung cancer, and resistance typically develops during the course of the treatment. Therefore, understanding biomarkers which can predict resistance to EGFR-TKI is important. Overexpression of GLI causes activation of the Hedgehog (Hh) signaling pathway and plays a critical role in oncogenesis in numerous types of cancer. In the present study, the role of GLI1 in erlotinib resistance was investigated. GLI1 mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and immunohistochemistry (IHC) in lung cancer cell lines and tumor specimens, respectively. GLI1 mRNA expression levels were found to be positively correlated with the IC50 of erlotinib in 15 non-small cell lung cancer (NSCLC) cell lines. The downregulation of GLI1 using siRNA sensitized lung cancer cells to the erlotinib treatment, whereas the overexpression of GLI1 increased the survival of lung cancer cells in the presence of erlotinib, indicating that Hh/GLI activation may play a critical role in the development of TKI resistance in lung cancer. Combined treatment with erlotinib and a GLI1 inhibitor reduced the cell viability synergistically. A retrospective study of patients with NSCLC treated with erlotinib revealed that those with a high IHC score for GLI1 protein expression had a poorer prognosis. These results indicated that GLI1 is a key regulator for TKI sensitivity, and patients with lung cancer may benefit from the combined treatment of TKI and GLI1 inhibitor.

Dexamethasone inhibits stemness maintenance and enhances chemosensitivity of hepatocellular carcinoma stem cells by inducing deSUMOylation of HIF­1α and Oct4.

It has been controversial whether patients with hepatocellular carcinoma (HCC) should receive glucocorticoid therapy during chemotherapy. Recent studies have demonstrated that glucocorticoids increase the therapeutic sensitivity of tumors to some chemotherapeutic drugs, but the specific mechanism remains unclear. In the present study, dexamethasone (Dex) was used to treat HCC stem cells. The results demonstrated that Dex reduced stemness maintenance and self­renewal of HCC stem cells, promoted epithelial­to­mesenchymal transition, inhibited migration and angiogenesis and, more importantly, increased cell sensitivity to the herpes simplex virus thymidine kinase/ganciclovir drug system in vitro and in vivo. Further mechanistic analyses demonstrated that Dex inhibited small ubiquitin­like modifier (SUMO) modification of several proteins in HCC stem cells, including hypoxia­inducible factor (HIF)­1α, an important hypoxia tolerance protein, and octamer­binding transcription factor 4 (Oct4), a crucial stemness maintenance protein. Inducing deSUMOylation of HIF­1α and Oct4 reduced their accumulation in the nucleus, thereby inhibiting tumor angiogenesis and stemness maintenance. These findings provide a new perspective to the study of the mechanism underlying the anti­hepatocarcinogenesis effects of Dex. Due to the few side effects of glucocorticoids at low doses and their anti­inflammatory effects, the appropriate combination of glucocorticoids and chemotherapeutic drugs is expected to improve the survival of HCC patients and their prognosis.

SUVmax Ratio on PET/CT May Differentiate Between Lung Metastases and Synchronous Multiple Primary Lung Cancer.

PURPOSE: To investigate the features of 18F-Fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in differentiating synchronous multiple primary lung cancers (sMPLC) from intropulmonary metastasis (IM). MATERIAL AND METHODS: Fifty-nine patients with two synchronous primary lung cancers were selected and 23 lung cancer patients with an additional solitary IM cancer were chosen as the control group between January 2009 and January 2019. Maximum standardized uptake values (SUVmax) on PET/CT was determined for each tumor. The SUVmax ratio between the two tumors was determined and receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. RESULTS: The difference of SUVmax ratio between sMPLC (2.3 ± 1.6) and IM (1.5 ± 0.4) was significant, p < 0.01; the area under the curve of the SUVmax ratio was 0.78 with the optimal cutoff value 1.7 (sensitivity 62.7% and specificity 82.6%, p < 0.001). CONCLUSION: The SUVmax ratio between two tumors may be helpful in differentiating sMPLC from IM, independent studies with bigger size were needed to further confirm the findings.

Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal cancer patients.

KRAS is an independent negative predictor for anti-epidermal growth factor receptor (anti-EGFR) treatment in colorectal cancers (CRCs). However, 30% to 50% of CRC patients are KRAS-positive and do not benefit from anti-EGFR therapy. In this study, we investigated the mutational features and clinical significance of KRAS-positive Chinese CRC patients. A total of 139 Chinese CRC patients who received clinical KRAS testing (Sanger sequencing) were examined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Fifty KRAS-positive specimens were further detected by next-generation sequencing (NGS). The most prevalent mutation in KRAS was G12D (46%), followed by G12V (20%), and G13D (18%). In addition to KRAS, 72 unique alterations in another 12 genes were also detected. The most common mutated genes were TP53 (62%), APC (46%), and PIK3CA (22%). The proportion of HER2 amplifications in KRAS-positive CRC patients was 4.4%, which was lower than that in KRAS -negative CRC patients (14.3%). No relationship was found between HER2 amplification and KRAS status (p = 0.052). However, the odds ratio is very low (0.279). In addition, these gene mutations were not significantly associated with age, sex, tumor size, lymph node metastasis, mismatch repair-deficient, or tumor differentiation. However, TP53 mutations were more prevalent in colon cancer with KRAS mutations than in rectal cancer (75.0% vs 28.6%, respectively, p = 0.004). The negative predictive value of the IHC analysis for predicting HER2 amplification reached to 98.39%, while the positive predictive value reached only 50%. Overall, the mutation profiling of Chinese CRC patients with KRAS mutations is different from that of Western CRC patients. Our results will help us to understand the molecular features of Chinese CRC patients.

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

Expression of miR-551b and its effect on apoptosis in human gastric carcinoma.

miR-551b has been reported to be involved in tumorigenesis, cell invasion, and metastasis in gastric cancer but the mechanism remains unclear. In this study, in an attempt to address this question, we examined expression of miR-551b in gastric tumors and adjacent normal tissue. We transfected SGC-7901 gastric cancer cells with miRNA non-sense sequences (NC group), miR-551b mimics (miR-551b mimic group), and miR-551b inhibitors (miR-551b inhibitor group) to investigate the role of miR-551b in autophagic apoptosis. In gastric tissue, our real-time PCR results revealed that expression of miR-551b was significantly downregulated and the relative expression of miR-551b (1.75 ± 0.13) was significantly lower than in normal tissue (2.47 ± 0.38) (P<0.05). In transfected SGC-7901 cells, compared with the NC and miR-551b inhibitor group, miR-551b expression level and apoptosis rate in miR-551b mimics group was significantly increased whereas proliferation and invasion rates were significantly decreased (P<0.05). Hoechst 33342 fluorescence staining showed that a large number of autophagosomes were detected in miR-551b mimic group, fewer in the NC group, and only a small number in miR-551b inhibitor group. Western blotting showed that expression levels of NF-κB, LC3 II, and Beclin 1 in miR-551b mimics group were significantly higher than in the NC group and miR-551b inhibitor group (P<0.05). Our findings suggest that miR-551b could inhibit proliferation, apoptosis, and invasion of gastric cancer cells and the action mechanism may be related to induction of gastric cancer cells autophagic apoptosis.

Expression and clinicopathologic significance of TUFM and p53 for the normal-adenoma-carcinoma sequence in colorectal epithelia.

BACKGROUND: Evidence indicates that most cases of colorectal carcinoma (CRC) develop from adenoma. A previous study demonstrated that mitochondrial Tu translation elongation factor (TUFM) might serve as an independent prognostic factor for colorectal cancer. However, the expression and function of TUFM in the normal-adenoma-cancer sequence have not been reported. In this study, we investigated the clinicopathologic significance of TUFM and p53 expression for the normal-adenoma-carcinoma sequence in colorectal epithelia and evaluated the roles of TUFM during the progression of colorectal tumors. METHODS: Paraffin-embedded specimens from 261 colorectal normal mucosa samples, 157 adenomas, and 104 early carcinomas were analyzed for TUFM and p53 expression by immunohistochemistry. RESULTS: Expression of TUFM and p53 was significantly increased during the colorectal normal-adenoma-carcinoma sequence (all P < 0.05). The expression of TUFM and p53 was associated with histologic type of adenomas (P = 0.028; P = 0.001) and grade of dysplasia (all P = 0.001). Expression of TUFM was positively correlated with that of p53 (r = 0.319, P = 0.001). CONCLUSIONS: Upregulated TUFM expression may play an important role in the transformation from colorectal normal mucosa to carcinoma through adenoma. Combined immunohistochemical detection of TUFM and p53 may be useful for evaluating the biological behavior of colorectal adenoma.

Expression of ASPM in colonic adenocarcinoma and its clinicopathologic significance.

BACKGROUND: ASPM is a newly reported stem cell marker and plays important roles in mitosis, cell cycle and tumorigenesis. It links with poor clinical prognosis in various tumors. However, the clinical significance of ASPM in colonic adenocarcinoma (CA) has not been fully studied. The purpose of this study was to investigate if ASPM is correlated with the clinicopathological features of CA. METHODS: Primary CA tissue, adenoma and the matched normal mucosa from 99 patients, were detected using immunohistochemical analysis by primary antibodies against ASPM. Meanwhile, 20 CAs and 20 liver metastatic cases were examined by RNA in situ hybridization (RNAscope). To assess the clinical relevance of ASPM, we analyzed the survival follow-up information. RESULTS: ASPM was found only in single cells in the base of normal colon mucosal crypts. But the expression of ASPM was detected high in colonic adenomas (49.5%, 49/99), and significantly higher in CA (56.6%, 56/ 99, P<0.001). In CAs, ASPM expression was more intense in stage III and IV than II and I stage patients (P=0.03), and positively correlated with lymph node metastasis (P=0.03), but not with the age at diagnosis, gender and histological grade (P>0.05). We also analyzed the survival follow-up information, the data showed that ASPM-positive expression was correlated with a shorter disease-free survival (DFS) time, the average DFS time of patients with ASPM positive and negative expression was 62.79±2.32 months and 71.30±2.72 months, respectively, and there was no statistical significance between the two groups (P>0.05). The results of ASPM mRNA measurement by RNAscope revealed ASPM mRNA expression was higher in primary CA than that in metastatic liver CA (P<0.001). CONCLUSIONS: ASPM might play an important role in colonic carcinogenesis and be a potential marker in predicting prognosis of CA.

Aberrant LRP16 protein expression in primary neuroendocrine lung tumors.

BACKGROUND: The Leukemia related protein 16 gene (LRP16) localized on chromosome 11q12.1, is an important estrogen-responsive gene and a crucial regulator for NF-kB activation. LRP16 is frequently expressed in human cancers; however, the LRP16 gene remains unexplored in lung neuroendocrine tumors. The aim of this study was to investigate the role of LRP16 expression in primary lung neuroendocrine tumors. METHODS: lung neuroendocrine tumors were analyzed for LRP16 gene expression by two-step non-biotin immunohistochemical method. RESULTS: Fifty of ninety (55.6%) cases of neuroendocrine lung tumors tested were positive for LRP16 protein by immunohistochemistry. The expression of LRP16 was mainly located in cytoplasm and nucleus of tumor cells. LRP16 protein was corresponding to tumor type and clinical stage, as well as survival time. CONCLUSIONS: The results indicate that abnormal LRP16 expression is noted in neuroendocrine lung tumors and the expression can give insight into the pathogenesis of the disease. The LRP16 protein may serve as a potential marker in predicting prognosis of neuroendocrine lung tumors.

Correlation of decreased expression of PHLDA1 protein with malignant phenotype of gastric adenocarcinoma.

BACKGROUND: Gastric carcinoma is one of the most aggressive malignancies with an extremely poor prognosis. Recent findings suggest decreasing PHLDA1 (pleckstrin-homologylike domain family A, member1) expression plays a significant role in inhibiting cell migration and tumor invasion. The clinicopathological significance of the expression of PHLDA1 in gastric carcinoma remains to be determined. METHODS: PHLDA1 protein was investigated by immunohistochemistry for the expression status in 336 cases of gastric adenocarcinomas and 60 normal mucosa, and then the results were analyzed with the patient's age, sex, tumor site, size and the histological grade, clinical stage as well as overall median survival time. RESULTS: The expression of PHLDA1 protein was obviously decreased in 57.1% of gastric carcinomas. Carcinomas with loss of expression of PHLDA1 were significantly corresponding to with tumor size (P=0.037), grade (P=0.028), depth of invasion (P=0.001), lymph node metastasis (P=0.008) and stage (P=0.001) but not with age (P=0.194), sex (P=0.312), tumor site (P=0.287) and distal metastasis (P=0.331) respectively. Follow-up data showed that there was a significant difference in overall median survival time between the carcinomas with PHLDA1 negative expression (31.0 months) and those with positive expression (54.0 months) (P=0.001). CONCLUSIONS: Our findings suggest that the decreased expression of PHLDA1 may play an important role in tumor progression, and may become a new adjunct biomarker in the prognosis in gastric carcinoma. A potential role for PHLDA1 in the early detection/or therapy of gastric cancer warrants further investigation.

Decreased expression of TFPI-2 correlated with increased expression of CD133 in cholangiocarcinoma.

BACKGROUND: Recent findings suggest decreasing TFPI-2 expression plays a significant role in inhibiting cell migration and tumor invasion. The clinicopathological significance of the expression of TFPI-2 and its possible correlation with the expression of CD133 in cholangiocarcinoma remains to be solved. METHODS: We investigated if TFPI-2 was involved in the clinicopathological significance of cholangiocarcinoma. An immunohistochemical method was used to detect 218 cases of cholangiocarcinoma, 30 para-neoplastic and 20 normal bile ducts for their expression status of TFPI-2 and CD133, and then the results were analyzed with the patient's age, sex, tumor site and the histological grade, clinical stage as well as overall mean survival time. RESULTS: Compared with the para-neoplastic and normal cholangiocytes, the expression of TFPI-2 was obviously decreased while the expression of CD133 in carcinoma cells was increased. Carcinomas with low expression of TFPI-2 were significantly corresponding to the tumor site (P = 0.006), size (P = 0.005), histological grade (P = 0.0001) and clinical stage (P = 0.0001), but not to the age (P = 0.066) and sex (P = 0.411), respectively. By Kaplan-Meier survival analysis, the low expression of TFPI-2 was significantly correlative with the overall survival time (P = 0.0001). Further, the expression of TFPI-2 was found inversely correlative with the expression of CD133 (g = -0.3876, P < 0.0001). CONCLUSIONS: Our finding suggests that the decreased expression of TFPI-2 may play an important role in the carcinogenesis and progression, and may become a new adjunct marker in the diagnosis and prognosis in cholangiocarcinoma. The expression of TFPI-2 may be inversely correlative with the expression of CD133.

Predictive value of CHFR and MLH1 methylation in human gastric cancer.

BACKGROUND: Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. METHODS: The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan-Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. RESULTS: The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3% (35/102), 21.6% (22/102), 12.7% (13/102), 9.8% (10/102), and 0% (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95% CI, 0.069-0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95% CI, 1.064-8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). CONCLUSIONS: CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was related to oxaliplatin resistance in gastric cancer patients.

[Clinical features of inflammatory myofibroblastic tumor in the head and neck].

OBJECTIVE: To summarize the clinical characteristics of inflammatory myofibroblastic tumor (IMT) in head and neck and to discuss its treatment. METHODS: Twenty-seven cases of IMT in head and neck diagnosed at the Chinese PLA General Hospital from 2004 to 2012 were analyzed retrospectively. Among the 27 patients, 12 males and 15 females, age ranged from 8 to 77 years, with a median 43 years old. Treatment included: 1 with radiotherapy, 22 with surgery, 3 with surgery and postoperative radiotherapy, one with concurrent chemoradiotherapy followed by surgery. Of the 27 cases, 5 located in the neck, 6 in the nasal and paranasal sinus, 4 in the temporal bone, 3 in the throat, 2 in the parotid gland, 2 in the lower pharynx, 1 in the mandible, 1 in the maxilla, 1 in the masseter muscle, 1 in the amygdala and 1 in the pharynx nasalis. RESULTS: Following-up time was 4-85 months, with a median of 26 months. Six cases lost follow-up, 1 case with malignant transformation and died, 16 cases survived with no recurrence, 4 cases relapsed, of whom 2 were alive with tumors and 2 died. CONCLUSIONS: IMT in the head and neck has a tendency to be malignancy, with certain recurrence rate and mortality. Radical excision is still the first choice of treatment for IMT in head and neck.

Identification of a tumor-suppressive human-specific microRNA within the FHIT tumor-suppressor gene.

Loss or attenuated expression of the tumor-suppressor gene FHIT is associated paradoxically with poor progression of human tumors. Fhit promotes apoptosis and regulates reactive oxygen species; however, the mechanism by which Fhit inhibits tumor growth in animals remains unclear. In this study, we used a multidisciplinary approach based on bioinformatics, small RNA library screening, human tissue analysis, and a xenograft mouse model to identify a novel member of the miR-548 family in the fourth intron of the human FHIT gene. Characterization of this human-specific microRNA illustrates the importance of this class of microRNAs in tumor suppression and may influence interpretation of Fhit action in human cancer.

[Clinicopathological significance of abnormal metabolism of polyunsaturated fatty acids in colorectal cancer tissue].

OBJECTIVE: To explore the relationship between different tissue levels of polyunsaturated fatty acid (PUFA) and the clinicopathologic parameters in colorectal carcinoma (CRC) and evaluate their prognostic significance. METHODS: Fresh frozen malignant tissue was obtained from 82 colorectal cancer patients at PLA general Hospital from December 2010 to March 2011. The immunohistochemical results were obtained for vascular endothelial growth factor (VEGF), P53 and Ki-67. The relationship between the PUFA level and such clinicopathological profiles as age, gender, location, differentiation degree, TNM (tumor, node and metastasis) stage, VEGF, Ki-67 and P53 was analyzed. RESULTS: Tissue level of arachidonic acid (AA) in patients aged over 60 years (n = 44) was significantly lower than those under 60 years (n = 38) (0.12% ± 0.06% vs 0.17% ± 0.09%, P = 0.045). In patients with tumor size < 5 cm (n = 42), tissue level of EPA was significantly higher (0.29% ± 0.13% vs 0.20% ± 0.14%, P = 0.030) while ω-6/ω-3 PUFA lower (10.8 ± 2.6 vs 13.2 ± 6.4, P = 0.031). Significant statistical difference existed in tissue level of LA, AA/ω-3 PUFA in different differentiation degrees(P = 0.013, 0.027). Tissue level of linoleic acid(LA) in poorly differentiated tumor was the highest (19.9% ± 6.3%) while AA/ω-3 PUFA the lowest (4.1 ± 2.0, P < 0.05). Tissue level of LA was higher in VEGF-positive tumors than those in VEGF-negative counterparts(16.2% ± 3.7% vs 13.9% ± 2.7%, P = 0.009) while the ratios AA/ω-3 PUFA, AA/ω-6 PUFA, AA/LA in VEGF-positive tumors were lower than those in VEGF-negative counterparts (5.0 ± 1.8 vs 6.7 ± 3.3, 0.30 ± 0.09 vs 0.34 ± 0.09, 0.50 ± 0.21 vs 0.61 ± 0.21, P = 0.004, 0.038, 0.030) . In Ki-67 negative LA was highest (22.5% ± 10.1%, P = 0.048). No significant differences existed in the level of PUFA among the gender, the clinicopathological stage, lymph node metastasis and groups with differential expressions of P53 (all P > 0.05). CONCLUSIONS: The tissue levels of PUFA are somewhat correlated with the clinicopathologic parameters of CRC. And the prognosis of CRC may be evaluated through the test of PUFA.

Overexpression of carbonic anhydrase II and Ki-67 proteins in prognosis of gastrointestinal stromal tumors.

AIM: To investigate the expression and prognostic value of carbonic anhydrase II (CA II) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People's Liberation Army General Hospital from January 2004 to December 2010 were retrospectively followed up, and immunohistochemistry was used to detect CA II, Ki-67 and CD117 expression in tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. Log-rank test, χ² test and Cox proportional hazards model were used to determine the relationships between CA II, Ki-67 and CD117 expression and prognostic value in GISTs. RESULTS: The survival rates at 1, 3 and 5 years were 90.0%, 82.0% and 72.0% in all patients. However, in patients with positive CA II or Ki-67, the survival rates were 92.0%, 83.0% and 77.0% or 83.0%, 66.6% and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were significantly lower (CA II log-rank P = 0.000; Ki-67 log-rank P = 0.004). Multivariate Cox analysis revealed that CA II, CD117 and Ki-67 were considerable immune factors in prognosis of GIST patients (CA II P = 0.043; CD117 P = 0.042; Ki-67 P = 0.007). Besides, tumor diameter, mitotic rate, tumor site, depth of invasion, complete resection, intraoperative rupture, and adjuvant therapy were important prognosis predictive factors. Our study indicated that CA II had strong expression in GISTs and the prognosis of GISTs with high CA II expression was better than that of GISTs with low or no expression, suggesting that CA II is both a diagnostic and prognostic biomarker for GIST. CONCLUSION: CA II and Ki-67 are significant prognostic factors for GISTs. CA II associated with neovascular endothelia could serve as a potential target for cancer therapy.

Solid-pseudopapillary neoplasm of the pancreas: awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors.

Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm predominantly reported in young women. It classically presents as a large tumor with cystic and solid components. The major differential diagnosis includes pancreatic neuroendocrine tumor (PanNET). This study presents our experience with this tumor with emphasis on the morphologic features of the clear cell variant of SPN. Fifteen histologically confirmed SPN were identified in our files. Endoscopic ultrasound-guided fine needle aspirations (EUS-guided FNA) were performed in 8/15 cases. Patients' demographics, cytohistologic correlation and tumor characteristics were evaluated. Eleven of the 15 subjects were female and four were male with an age range of 17-73 years. Twelve SPN were located in the pancreatic body/tail, and three in the head. Tumor size ranged from 1.5 to 8.5 cm and 11 were solid. Of the eight EUS-guided FNA, four were diagnosed as SPN, two as SPN vs. PanNET, one as malignant with signet ring features, and one was nondiagnostic. Immunohistochemistry was performed on six/eight FNA cell blocks and 13/15 surgical specimens. Two of the 15 cases were classified as clear cell variants of SPN. Our study shows that SPN may occur in males and older adults, and present as a small or solid tumor. The clear cell variant of SPN, characterized by vacuolated cytoplasm and signet cell morphology, may pose a diagnostic challenge on FNA. Awareness of the wide spectrum of SPN clinical presentations, the morphology of its clear cell variant and the appropriate use of ancillary immunohistochemistry can prevent diagnostic errors.