Clinicopathological features of ovarian Brenner tumors / 中华病理学杂志

Objective@#To investigate the clinicopathological characteristics and diagnosis of ovarian Brenner tumors.@*Methods@#Forty-seven cases of ovarian Brenner tumors were enrolled from January 2012 to May 2018 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Clinical data, imaging examination, histopathological characteristics and immunohistochemical phenotype were analyzed.@*Results@#The age of the patients ranged from 30-73 years and the mean age was 55 years. Thirty-nine patients (83.0%) were postmenopausal. Forty cases (85.1%) of the Brenner tumors were benign, five (10.6%) borderline and two (4.3%) malignant. Usual tumor markers of ovarian carcinoma, including CA199 and CA125 were normal or mild elevated in the 47 cases. Imaging before surgery was not specific to Brenner tumors. Microscopically, benign Brenner tumors were composed of nests of bland, transitional-type cells within a fibromatous stroma. In our 5 cases of borderline Brenner tumors, mildly atypical transitional-type cells were projected into the cyst lumens and lack of stromal invasion. In 2 cases of malignant Brenner tumors, different degrees of nuclear atypial transitional-type cells exhibited stromal invasion. Immunohistochemical stains for CK7, GATA3, p63 and CK5/6 were positive in all cases. Ki-67 was less than 5% in Brenner tumors, and up to 20%-30% in malignant Brenner tumors.@*Conclusion@#Brenner tumors are mostly seen in postmenopausal patients and are usually benign. Imaging examination and usual ovarian tumor markers do not provide diagnostic value. Diagnosis and classification of Brenner tumors depend on histopathological evaluation.

Placental site nodule: a clinicopathological study of 20 cases / 临床与实验病理学杂志

Purpose To investigate the clinical manifesta-tions and morphologic features of placental site nodules (PSNs), and its clinical significance. Methods Twenty patients diag-nosed as PSNs were collected, then a retrospective analysis was conducted, and the characteristics of clinical data and follow-up results were analyzed,including of clinical manifestations, ultra-sonographic evaluation, morphologic and immunohistochemical features. Results The age of patients ranged from 25 to 41 years (32. 48 ± 4. 77 years in average). Three fifths of patients had pregnancy history for at least two times and the interval time to the last pregnancy ranged from 5 to 37 months (15. 33 ± 8. 05 months on average). 15 (75% ) patients went to the hospital because of abnormal vaginal bleeding. In our study, most of the samples showed a membrane-like structure without definite nod-ule. Microscopically, single or multiple, well-circumscribed and oval small nodules were found in endometrial tissue. In most ca- ses, the hyalinization was generally uniform in the center of the nodules, more or less intermediate trophoblasts appeared on the edge of the nodules. Immunohistochemically, the strong diffuse expressed CK (AE1/AE3), CAM5. 2, EMA, GATA-3, Cyclin E and p63 were detected in most of all cases, and PLAP showed strong focal expression, α-inhibin and hPL showed faint focal expression, Ki-67 staining for proliferative index was less than 4% . Conclusion PSN is a benign lesion of the intermediate trophoblast at the chorionic leave. Some diseases including hya-linized decidua, epithelioid trophoblastic tumor, and squamous cell carcinoma with hyalinization need to be identified. Some im-munohistochemical markers may be certain helpful in distinguis-hing as necessary.

Clinicopathological analysis of 5 cases of placental mesenchymal dysplasia / 临床与实验病理学杂志

Purpose To explore the clinicopathological features, diagnosis, differential diagnosis and prognosis of placental mesenchymal dysplasia. Method The clinicopathological data of 5 cases with placental mesenchymal dysplasia were retrospectively analysed and related literatures were also re-viewed. Results All of 5 patients were consciously fetal movement disappeared or found abnormal ultrasound results at routine examination of the pregnancy. The placentas were enlarged, partly with oedematous "grape-like" cysts. On histologic exami-nation, enlarged villi with varying degrees of edema contained abnormal thick walled fetal blood vessels. The chorionic vessels were expanded and congested, and some chorionic villi showed mesenchymal cell hyperplasia. In immunohistochemical staining, p57 was positive, and Ki-67 showed low expression. There was no the trophoblastic proliferation. It's mainly differential diagnosis was hydatidiform mole.2 cases were accompanied with stillbirth. Conclusion The diagnosis of placental mesenchymal dysplasia can be confirmed by pathology examination. When a cystic placenta is detected by ultrasound examination, placental mesenchymal dysplasia should be considered in the differential diagnosis.

KRAS mutations analysis in mucinous epithelial lesions of the endometrium / 中华病理学杂志

Objective@#To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features.@*Methods@#The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups.@*Results@#The patients′age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05).@*Conclusion@#The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.

Clinical application of STR genotyping diagnosis for hydatidiform mole and nonmolar gestation / 中华病理学杂志

Objective@#To investigate the value of short tandem repeat (STR) genotyping in the diagnostic workup of molar and non-molar gestations with correlation of histological characteristics.@*Methods@#Six hundred and fifty-six cases were selected based on clinically suspected hydropic abortion and/or molar pregnancy from July 2015 to September 2017 at Beijing Obstetrics and Gynecology Hospital. DNA was extracted from dissected chorionic villi and paired maternal endometrial FFPE tissue samples by Simplex OUP™ FFPE DNA Tissue Kit. STR genotyping was performed by PowerPlex 16 HS system.@*Results@#DNA genotyping was informative in 649 of 656 cases, leading to identification of 215 hydatidiform mole gestations and 434 non-molar gestations. Most of non-molar gestations (375 cases, 86.4%) were diploid hydropic abortion. Various trisomy syndromes were found (53 cases, 12.2%), including trisomy 2, 3, 4, 7, 8, 13, 16 and 21. Only 2(0.5%) digynic triploid gestations were detected. Moreover, 4 cases (0.9%) of uniparental disomies (homologous or heterologous) were found. There were 196 cases with histologic diagnostic suspicious of hydatidiform moles were accurate sub-classified. Among them, 59 cases hydatidiform moles were under-diagnosed as diploid hydropic abortions, and 28 cases diploid hydropic abortions were over-diagnosed as hydatidiform moles.Compared with partial moles(PHM), there were no specific histomorphological features between the various types of non-molar gestations and partial moles for definitive diagnostic separation. There was no significant difference in the expression of p57kip2 among PHM, trisomy and diploid hydropic abortions group (P=0.247).@*Conclusions@#STR genotyping can distinguish non-molar gestations from early hydatidiform moles, and efficiently avoid misdiagnosis based only on histological evaluation. Therefore, using STR genotyping, not only can the overdiagnosis of non-molar pregnancy be avoided, but also individualized management can be offered to patients including monitoring of serum hCG.

Value of detection of DNA mismatch repair proteins deficiency by immunohistochemistry in predicting tumor microsatellite status / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity and specificity of immunohistochemical (IHC) staining of DNA mismatch repair (MMR) protein for the screening of microsatellite instability (MSI) colorectal cancer (CRC).</p><p><b>METHODS</b>A total of 255 CRC cases were studied, including 140 cases of routine paraffin-embedded tissue samples and 115 cases constructed on tissue microarray. Expressions of 4 MMR proteins including MHL1, MSH2, MSH6 and PMS2 were investigated by IHC. Negative protein expression was defined as complete absence of nuclear staining within tumor cells in the presence of positively labeled internal non-neoplastic cells. Focal staining was defined as the presence of staining in < 5% of the tumor cells. CRCs showing negative staining for any MMR proteins were interpreted as MMR deficient tumors. PCR-genescan MSI analysis was performed in each case by a five marker panel including Bat26, Bat25, NR-21, NR-24 and MONO-27.</p><p><b>RESULTS</b>Among the 140 CRCs with routine formalin-fixed paraffin embedded tissue sections, concordance rate between IHC and PCR-genescan was 98.6% (138/140), the sensitivity and specificity of IHC in detecting MSI tumors were 94.9% (37/39) and 100.0% (101/101), respectively. The 2 disconcordant cases showed focal staining in at least one of the MMR proteins but were confirmed to be MSI-H CRCs by PCR-genescan assay. On tissue microarray, 91.3% (105/115) of the cases had informative results. The concordance rate between IHC and PCR-genescan was 100.0% (105/105). Both the specificity and sensitivity of IHC in detecting MSI tumors on available tissue microarray samples were 100.0%. Ten cases were inclusive due to the presence of negative stains of MMR proteins in both the tumor and internal control cells.</p><p><b>CONCLUSIONS</b>Detection of 4 MMR proteins expression by IHC is reliable for identifying MSI CRCs and is recommended for routine practice. Tumors with focal MMR protein staining are highly suspected for the presence of MSI-H and PCR-genescan based MSI analysis should be performed to confirm.</p>

Diagnostic utility of STR genotyping for partial hydatidiform moles / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinical utility of short tandem repeats(STR) genotyping technique for diagnosis of partial hydatidiform moles (PHM).</p><p><b>METHODS</b>Ten cases with the original diagnosis of PHM and six cases diagnosed as "favour PHM" or "abnormal villous, PHM not excluded" were selected for the study. The clinical information and follow-up data were reviewed. Histopathologic features were evaluated along with p57 immunohistochemistry. After DNA extraction from each sample, genotyping was performed by AmpFlSTR(®) Identifiler™ PCR kit to amplify 15 STR polymorphism loci plus the amelogenin gender-determining in a single robust PCR.</p><p><b>RESULTS</b>The age of patients ranged from 18 to 49 years (mean=29 years, median=29 years). Two villous populations (7/16), irregular villous contour (13/16), at least moderate trophoblastic hyperplasia (2/16), cistern formation (8/16), syncytiotrophoblastic knuckles (14/16), trophoblastic pseudoinclusions (6/16) and nucleated fetal red blood cells (8/16) were presented in these cases. Of the cases in the study, STR genotyping identified 4 monospermic complete hydatidiform moles (MCM), 3 dispermic partial hydatidiform moles (DPM) and 9 hydropic abortions (HA). The misdiagnosis rate was 13/16 only relied on morphology evaluation. Immunostaining of p57 showed 3/4 of MCM were focally positive (<5%-20%+), 1/4 of MCM were diffusely positive (70%+), 3/3 of DPM were diffusely positive (≥50%+), 7/9 of HA were diffusely positive (≥50%+), and 2/9 of HA were focally positive (10%+).</p><p><b>CONCLUSIONS</b>Combination of histomorphologic evaluation and p57 immunostaining is insufficient for a definitive diagnosis of PHM. STR genotyping offers an accurate diagnosis of PHM.</p>

Relationship between p53 Arg72Pro polymorphism and cervical carcinoma in Uigur and Han women in Xinjiang / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the association between p53 Arg72Pro polymorphism and cervical carcinomas HPV-associated cervical carcinoma in Uigur and Han women.</p><p><b>METHODS</b>The distribution and frequencies of p53 Arg72Pro genotypes were determined by PCR-RFLP in 152 cases of cervical carcinoma in ethnic Uigur women with 110 cases of normal control and 120 cases of cervical carcinoma in Han women with 122 cases of normal control.</p><p><b>RESULTS</b>The omni-constituent ratio of p53 genotype was statistically different between cervical carcinoma and normal control groups in the Uigur (chi(2) = 7.196, P < 0.05) group. The proportion of Arg/Arg was higher in cervical carcinomas than that in control. The omni-constituent ratio of p53 genotype was statistically different between cervical carcinoma and normal control groups in Han (chi(2) = 8.231, P < 0.025). The proportion of Pro/Pro was higher in cervical carcinoma than that in normal control. The omni-constituent ratio was statistically different between HPV 16 positive and negative groups of cervical carcinoma in the Uigur group (chi(2) = 7.177, P < 0.05). The proportion of Arg/Arg was higher in HPV 16 positive group than that in HPV 16 negative group.</p><p><b>CONCLUSIONS</b>p53 Arg72Pro polymorphism may be associated with the development of cervical carcinoma in Uigur and Han women in Xinjiang. p53 Arg/Arg genotype may be a genetically susceptible factor to HPV-associated cervical carcinoma in Uigur. p53 Pro/Pro genotype may be a genetically susceptible factor to cervical carcinoma in Han. There may be different susceptibilities to cervical cancer between Uigur and Han women in Xinjiang.</p>

Impact of elevated CO2 concentration under three soil water levels on growth of Cinnamomum camphora / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Forest plays very important roles in global system with about 35% land area producing about 70% of total land net production. It is important to consider both elevated CO(2) concentrations and different soil moisture when the possible effects of elevated CO(2) concentration on trees are assessed. In this study, we grew Cinnamomum camphora seedlings under two CO(2) concentrations (350 micromol/mol and 500 micromol/mol) and three soil moisture levels [80%, 60% and 40% FWC (field water capacity)] to focus on the effects of exposure of trees to elevated CO(2) on underground and aboveground plant growth, and its dependence on soil moisture. The results indicated that high CO(2) concentration has no significant effects on shoot height but significantly impacts shoot weight and ratio of shoot weight to height under three soil moisture levels. The response of root growth to CO(2) enrichment is just reversed, there are obvious effects on root length growth, but no effects on root weight growth and ratio of root weight to length. The CO(2) enrichment decreased 20.42%, 32.78%, 20.59% of weight ratio of root to shoot under 40%, 60% and 80% FWC soil water conditions, respectively. And elevated CO(2) concentration significantly increased the water content in aboveground and underground parts. Then we concluded that high CO(2) concentration favours more tree aboveground biomass growth than underground biomass growth under favorable soil water conditions. And CO(2) enrichment enhanced lateral growth of shoot and vertical growth of root. The responses of plants to elevated CO(2) depend on soil water availability, and plants may benefit more from CO(2) enrichment with sufficient water supply.