Purpose:To study the expressions of cyclin E and P53 in gastric carcinoma in relation to biological behavior and prognosis.Methods:Cyclin E and P53 expressions at protein level were determined by immunohistochemistry technique in 128 patients with gastric carcinoma.Results:Of the 128 patients , cyclin E positive expression was in 57(44 5%),P53 positive expression was in 67(52.3%),P53 and cyclin E were both positive in 48(37.5%),respectively.Cyclin E and P53 expression level were correlated with tumor size , invasion depth, regional lymph node status, vessel invasion, and distant metastasis, Univariate analysis demonstrated better survival in patients with negative cyclin E and P53 expressions than those with positive expression. By COX multivariate analysis, cyclin E expression level was found to be of independent prognostic significance, however p53 expression level was not found to be of independent prognostic significance.Conclusions:Cyclin E expression within gastric carcinoma tissues is an indicator of tumor behavior and prognosis, p53 expression within gastric carcinoma tissue is only an indicator of tumor behavior. [

Human milk plays an irreplaceable role in nutrition, immune promotion and psychological development of infants.And it can also decrease the risk of infectious disease, overweight/obesity, diabetes and other diseases.Therefore, the guidelines of various countries advocate that human milk is the optimal choice for infants.However, cases of food allergy in infants fed with human milk are common in clinical practice.Some studies have found that there are some active food antigens in human milk, which can stimulate immune responses and cause allergic symptoms in infants.At present, the mechanism of food allergy in infants fed with human milk is not clear, and this paper is to review the progress in this field in recent years.

AIM:To screen the gene expression profiles of normal gastric mucosa,primary gastric cancer and metastatic lymph nodes by gene expression microarray and the associated genes with lymph node metastasis by bioinformatics. METHODS:The differentially expressed genes of nontumorous gastric mucosa (group A),primary gastric cancer (group B) and metastatic lymph nodes (group C) were screened by gene expression microarray obtained from Affymetrix company. The results were further analyzed by bioinformatic software including Gene Expression Profiles Analysis of Cohort Experiment,Gene Ontology Enrichment Analysis and Pathway Significant Analysis. The expression of TLN1 in group A,B and C were confirmed by real-time reverse transcription PCR. RESULTS:278 genes were persistent up-regulated in group A,B,C,which participated mainly in immunologic responses,cell adhesion,phosphate transport,inorganic anion transport,cell chemotaxis,cell motility and signal transduction. While 387 genes were persistent down-regulated in group A,B,C,which were concerned with digestion,glucide metabolism,lipid metabolism,protein metabolism,one-carbon compound metabolism,nitrogen compound catabolism and cell adhesion. The pathway analysis suggested that integrin-mediated cell adhesion pathway were abnormally regulated. These genes including THBS1,TLN,CAPN3,ITGAX,SORBS1,CAPN6,CAPN9 were continuous up-regulated or down-regulated in integrin-mediated cell adhesion pathway. The expressions of TLN1 in group A,B,C were 0.0000342?0.0000711,0.1064?0.1251 and 0.2886?0.3529,respectively. The expression of TLN1 in metastatic lymph nodes was significantly higher than that in nontumorous gastric mucosa and primary gastric cancer (P

Objective To investigate the mRNA expression of UPA and MMP-9 in gastric carcinoma and their correlation with histological type, growth-type, differentiation, vessel invasion, metastasis and prognosis. MethodsIn situ hybridization was used to detect the mRNA expression of UPA and MMP-9. ResultsIn situ hybridization revealed that among 105 cases, the positive rates of UPA mRNA and MMP-9 mRNA were both 58.1%. There was no significant relationship between UPA mRNA and histological type( r _ s = 0.123, P =0.210)and differentiation ( r _ s =0.102, P =0.298)of the tumor. However, there was a significant difference between growth-type( r _ s =0.344, P =0.001),tumor invasion depth( r _ s =0.296, P =0.002),vessel invasion( r _ s =0.198, P =0.042),lymph node( r _ s =0.332, P =0.001)and distant metastasis( r _ s =0.530, P =0.001);there was no significant relationship between MMP-9 mRNA staining and histological type( r _ s =0.143, P =0.145)and differentiation( r _ s =0.102, P =0.298)of the tumor. However, there was a statistically significant difference between growth-type( r _ s =0.267, P =0.006),tumor invasion depth ( r _ s =0.335, P =0.001)、vessel invasion( r _ s =0.209, P =0.032),lymph node( r _ s =0.343, P =0.001)and distant metastasis( r _ s =0.468, P =0.001);There was a positive relationship between UPA mRNA and MMP-9 mRNA expression( r _ s =0.237, P =0.015). The mean survival time in cases with positive UPA mRNA and MMP-9 mRNA expression were significantly shorter than that of cases with negative expression. ConclusionThe mRNA expression of UPA and MMP-9 can predict the invasion and metastasis of gastric carcinoma, They can be used as markers of prognosis of gastric carcinoma in clinical practice.

Objective: To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor. Methods: Two cases of malignant gastrointestinal neuroectodermal tumor were retrieved; the clinical and radiologic features, histomorphology, immunophenotype, molecular genetics and prognosis were analyzed and the relevant literature reviewed. Results: Case 1 was a 57-year-old male, presented with recurrent abdominal pain and melena. Pelvic imaging showed a circumscribed thickening of the wall of a small intestinal segment, and a malignant lymphoma was favored. Case 2 was a 24-year-old male, presented with recurrent small intestinal malignancy. Imaging demonstrated multiple masses in the peritoneal and pelvic cavities, and a malignant gastrointestinal stromal tumor with multiple metastases was suspected. Grossly both tumors were located mainly in the muscularis propria of small intestine. Case 1 showed a single 5.5 cm tumor; and case 2 consisted of two tumors measuring 4 cm and 6 cm respectively. Microscopic examination of both tumors showed small round blue, but focally spindled or clear tumor cells in solid pattern. The tumor cells had scanty cytoplasm, indistinctive nucleoli and brisk mitoses. Osteoclast-like giant cells were dispersed within the stroma. In case 1 rosette-like and pseudo-papillary growth patterns were noted, and in case 2 there were variable-sized hemorrhagic cysts. By immunohistochemistry, both tumors showed strong and diffuse expression of SOX10 and S-100, and focal to diffuse expression of neuroendocrine markers (CD56 or synaptophysin). Case 2 exhibited focal reactivity to pan-cytokeratin. Both tumors lacked expression of markers associated with gastrointestinal stromal tumor, smooth muscle tumor, melanoma (HMB45 or Melan A), dendritic cell tumor and Ewing sarcoma. Fluorescence in situ hybridization analysis demonstrated EWSR1 rearrangement in both tumors and the next generation sequencing confirmed EWSR1-ATF1 gene fusion in case 2. At follow-up of 16 months, case 1 was recurrence or metastasis free; whereas case 2 showed multiple recurrences and metastases within 19 months although stable disease was transiently achieved when treated with combinations of multidrug and targeted chemotherapy. Conclusions Malignant gastrointestinal neuroectodermal tumor is a rare and aggressive soft tissue sarcoma with a predilection for small intestine. It has distinctive morphologic, immunohistochemical and molecular characteristics and needs to be distinguished from other small blue round and spindle cell tumors that occur in the gut. Careful attentions to its characteristic histomorphology with the judicious use of immunohistochemistry and molecular genetics can help to distinguish this tumor from its many mimickers.

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People′s Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, β-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

Objective: To investigate the molecular genetic and clinicopathologic characteristics, immunophenotypes, diagnostic and differential diagnostic features of myxoid angiomatoid fibrous histiocytoma (MAFH). Methods: Three cases of MAFH were collected from the archives of Zhejiang Provincial People′s Hospital between January 2015 to August 2018. The clinical and radiologic features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed. Results: Patients consisted of 2 women and 1 man aged 37 years, 46 years, and 57 years, respectively. The clinical manifestations of 3 patients were presented as a painless, slowly-enlarged mass with a duration ranging of 2 weeks, 2 months and 50 years. These tumors were located at the deep somatic soft tissue of extremities or limbs (right hip, left forearm, left wrist, respectively) and 2 were preoperatively considered as ganglion cyst or giant cell tumor of tendon sheath by imaging examinations. The diameter of circumscribed mass lesion was ranged from 3.0 to 7.5 cm, which exhibited a gray white to tan and gelatinous cut surface. Extensive hemorrhage and cystic changes were observed in 2 cases. Under low magnification, all tumors showed a dense fibrous pseudo-capsule with a peritumoral lymphoplasmacytic cuff and a multi-nodular growth pattern. Blood-filled cystic spaces were observed in 2 tumors. The myxoid stroma occupied 60.0%, 80.0% and 90.0% area of the entire tumor, respectively. Within the myxoid areas, tumor cells were oval to stellate and arranged in cord-like, microcystic and reticular growth patterns. Transitions of myxoid tumor components to more solid areas with typical histology of angiomatoid fibrous histiocytoma (AFH) were observed at least focally in all the three cases. The tumor cells exhibited minimal atypia and scarce mitoses (1 to 2/50 HPF) without necrosis, and prominently focal intracytoplasmic vacuoles were identified in one case. The results of immunohistochemistry staining showed that, 2/3 cases focally expressed desmin, 2/3 focally expressed epithelial membrane antigen (EMA), and 1/3 focally expressed CD99. The positive index of Ki67 was approximately 1% to 5%. Fluorescence in situ hybridization analysis showed that EWSR1 gene rearrangement occurred in all of the three cases. During the period of follow-up, one case showed local recurrence at 15 months, one case showed postoperative recurrence at 24 months, and the recurrent tumor slowly grew for 120 months until the second resection, without recurrence at the following 2 months. The left case showed a disease-free survival at 32 months. Conclusions MAFH is a rare subtype of AFH with a low-grade behavior and may lead to diagnostic confusions. Carefully searching for the typical AFH histomorphology and combining with EWSR1 gene rearrangement test can help to distinguish MAFH from other mimickers.

Objective: To investigate the histomorpholgic spectrum, immunophenotypic, and molecular genetic features of Sertoli cell tumor, not otherwise specified (SCT, NOS) of the testis. Methods: Seven cases of SCT, NOS of the testis were analyzed(4 from Peking University Third Hospital and 3 from Zhejiang Provincial People′s Hospital) between 2008 and 2017. The histopathologic features were examined based on HE staining, and EnVision method was used for immunohistochemistry staining of calretinin, inhibin, β-catenin, cyclinD1, CD10, CKpan, neuroendocrine markers, WT1, Melan A, vimentin, SALL4, GATA3, PAX8, and S-100 protein. Mutational analysis of exon 3 of the CTNNB1 gene by polymerase chain reaction (PCR)-amplified sequences and direct sequencing was performed. Results: Patients ages ranged from 22 to 65 years (mean 43 years). The clinical manifestation in all was a slowly enlarging, painless testicular mass.The maximum diameter of the tumor ranged from 1.5 cm to 3.0 cm (mean 2.1 cm). Sectioning usually disclosed a tan-gray to white mass with vague lobular cut-surface. Microscopically, the tumors were well circumscribed and non-encapsulated; the tumor cells were rearranged in multiple growth patterns from diffuse solid sheets to trabeculae and cords, ribbon and solid or hollow tubules setting in variable amount of acellular fibrous stroma. Two cases showed acellular collagenous stroma constituted >50% of the tumor confirming to the diagnosis of sclerosing SCT. One case demonstrated a prominent myxoid stromal change. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, 2 tumors had variable cells with abundant lipid-rich cytoplasm, and 1 other tumor showed scattered aggregates of multinucleated tumor cells. The tumor cells were bland-appearing without any evidence of atypia, mitoses were noted in 2 tumors (both were 1/50 HPF), but necrosis was absent. Immunohistochemical staining results as follows: vimentin (diffuse, 7/7), CD10 (diffuse membrane, 7/7); diffuse β-catenin nuclear and cytoplasm staining in 5 of 7 cases, and all the 5 cases showed diffuse cyclin D1 nuclear staining, β-catenin membrane staining in 2 of 7 cases, CKpan (5/7, focal or diffuse), calretinin (focal, 5/6), inhibin (focal, 3/7), synaptophysin (focal, 2/6), CD56 (focal or diffuse, 4/5), WT1 (diffuse nuclear, 4/5), and S-100 protein (diffuse, 3/7), and chromogranin A, Melan A, PAX8, GATA3 and SALL4 all were negative. Molecular genetic studies of PCR and direct sequencing showed CTNNB1 mutations in 4 of 7 (4/7) cases, 4 of the four mutation-carrying cases showed diffuse β-catenin nuclear and cytoplasm immunoreactivity and diffuse cyclin D1 nuclear immunoreactivity in the tumor cells. Conclusions SCT, NOS of the testis typically shows significant heterogeneities in both morphology and immunohistochemistry, thus causing differential diagnostic confusions. Molecular analyses showed mutations of exon 3 of CTNNB1 in more than half of these tumors, and nuclear accumulation of β-catenin and over expression of cyclin D1 can be useful for the differential diagnosis of SCT, NOS.

Objective:To investigate the clinicopathological characteristics, and prognosis of appendiceal goblet cell adenocarcinoma(GCA).Methods:The clinical and pathological data of 21 GCA cases were retrospectively analyzed, and their pathological morphology, immunohistochemical phenotype, genetic alteration and clinical treatment and prognosis were studied.Results:Most of the 21 patients showed appendicitis, with appendectomy alone or extensive resection of the tumor, followed by chemotherapy. There were 12 low-grade and 9 moderate and high-grade patients by pathological examination, and tumor cells express CEA, CK20, SATB-2, Syn(19/21), CgA(18/21), CD56(18/21), Ki67(+,10%-50%),and one patient had mutations in the BRAF gene.Depth of tumor infiltration ( r=0.716, P<0.001), and TNM stage ( r=0.816, P<0.001) were all positively correlated with the grade of GCA. After 19 to 98 months of follow-up, one patient relapsed and one patient died. Conclusions:Appendiceal GCA is a kind of tumor with bidirectional differentiation characteristics. Its morphology and biological behavior lineage are relatively broad, especially the high level is more aggressive, hence more active treatment should be adopted.

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma (BSNS). Methods: Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. Results: There were 2 male and 1 female patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients. Microscopically, these tumors were un-circumscribed and composed of cellular spindle-shaped cells arranged in long and interlaced fascicles. A hemangiopericytoma-like growth pattern was frequently identified. The overlying hyperplastic respiratory epithelium invaginated down into the tumor forming a cystic (2 cases), glandular (1 case) structures and inverted in a papilloma-like (1 case)pattern, and foci of eosinophilic metaplasia were also noted in 2 of the three cases. The tumor nuclei were bland-appearing, mitoses were scarce and necrosis was absent. Immunohistochemically, the tumor cells showed co-expression of neural and myogenic markers in all the 3 cases, including that 3/3 showed diffuse and strong positivity of S-100 protein, 3/3 positivity of smooth muscle actin (1 diffuse and 2 focal), 1/2 diffuse positivity of calponin, 1/3 focal positivity of desmin, and 1/1 focal positivity of MyoD1.In addition, 1 detected for β-catenin showed focal nuclear positivity. None of the 3 showed positivity to cytokeratin, CD34 or SOX10 in the tumor cells.Ki-67 showed an index <5%, 10% and <2%, respectively. Fluorescence in situ hybridization analysis showed rearrangements of PAX3 gene in all 3 cases. In case 3, reverse transcription polymerase chain reaction, followed by Sanger sequencing, demonstrated an in-frame fusion between PAX3 and FOXO1.Follow-up information (range 3-15 months)showed no evidence of local recurrence or distant metastasis in three cases. Conclusions BSNS is a newly described entity which can be readily confused with a variety of benign and malignant spindle cell tumors encountered in the sinonasal cavity; immunohistochemistry co-expression of neural and myogenic markers and PAX3 gene rearrangement can help distinguish this tumor from its many mimickers.