Circulating tumor DNA in lung cancer: real-time monitoring of disease evolution and treatment response / 中华医学杂志(英文版)

Lung cancer is one of the leading causes of all cancer-related deaths. Circulating tumor DNA (ctDNA) is released from apoptotic and necrotic tumor cells. Several sensitive techniques have been invented and adapted to quantify ctDNA genomic alterations. Applications of ctDNA in lung cancer include early diagnosis and detection, prognosis prediction, detecting mutations and structural alterations, minimal residual disease, tumor mutational burden, and tumor evolution tracking. Compared to surgical biopsy and radiographic imaging, the advantages of ctDNA are that it is a non-invasive procedure, allows real-time monitoring, and has relatively high sensitivity and specificity. Given the massive research on non-small cell lung cancer, attention should be paid to small cell lung cancer.

Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma / 中华医学杂志(英文版)

Background@#Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue.@*Methods@#PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses.@*Results@#Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = -2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = -2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499-4.367, P = 0.001).@*Conclusion@#These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.

Signal Transducer and Activator of Transcription 3 for the Differentiation of Hepatocellular Carcinoma from Cirrhosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Overexpression and constitutive activation of signal transducer and activator of transcription (STAT) 3 have been suggested in the tumorigenesis of many human cancers, including multiple carcinomas, melanoma, and lymphoma. The diagnosis of hepatocellular carcinoma (HCC) in lobectomy specimens is usually straightforward, but distinguishing cirrhosis from well-differentiated HCC can be challenging in core biopsies. Our aims were to investigate the expression level of STAT3 and phosphorylated STAT3 (pSTAT3) in HCC and cirrhosis, and the application of STAT3 in the differential diagnosis of HCC and cirrhosis.</p><p><b>METHODS</b>Sixty cases were divided into three groups: patients with HCC only (Group 1), HCC and cirrhosis (Group 2), and cirrhosis only (Group 3). Formalin-fixed and paraffin-embedded tissue sections were stained immunohistochemically for STAT3, pSTAT3, and CD163. The values obtained from the tissue sections of each group were compared in statistical analysis.</p><p><b>RESULTS</b>STAT3 showed a high level in HCC and was a significant marker for differentiating HCC from cirrhosis (P < 0.0001). The odds ratio between HCC and cirrhosis increased 34.4 times when the intensity of STAT3 increased by 1 level. Spearman's correlation and Chi-square tests also demonstrated that expression level of STAT3 did not correlate with age, gender, or the presence of a cirrhotic background.</p><p><b>CONCLUSIONS</b>STAT3 staining differs significantly in HCC and cirrhosis. The findings reinforce the role of STAT3 in the tumorigenesis of HCC and provide a useful marker to differentiate HCC from cirrhosis in challenging liver biopsies.</p>

Comparison of Ultrasound Features of Primary Metastatic Papillary Thyroid Carcinoma and Recurrent/Persistent Metastatic Cervical Lymph Nodes / 中国医学科学院学报

Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 12015 to January 12016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.

Comparison of ultrasonic features between anaplastic thyroid carcinoma and papillary thyroid carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the difference of the ultrasonic features between anaplastic thyroid carcinoma and papillary thyroid carcinoma.</p><p><b>METHODS</b>The ultrasound data of 7 patients with histopathologically confirmed anaplastic thyroid carcinomas who were treated in PUMC Hospital from April 2001 to June 2014 were retrospectively studied. In addition, 21 sex-and age-matched patients with histopathologically confirmed papillary thyroid carcinomas during the same period were enrolled as the control group. The pathologic results were regarded as the gold standard. The ultrasonic features of anaplastic thyroid carcinoma and papillary thyroid carcinoma were analyzed and compared.</p><p><b>RESULTS</b>Patients with anaplastic thyroid carcinoma were predominantly females (5/7,71.4%), with an average age of (64.9 ± 11.3) years. Large mass [(5.17 ± 1.26) cm vs. (1.85 ± 1.89)cm, P<0.001], anteroposterior-to-transverse diameter ratio less than 1(100.0% vs. 47.6%, P ＝ 0.03), and punctuate calcification (100.0% vs. 52.4%, P ＝ 0.03) were more frequently associated with anaplastic thyroid carcinoma than with papillary thyroid carcinoma. No significant difference was observed between the two groups in the shape, margin, cystic change, echogenicity, echotexture,vascularity,and envelope (all P>0.05).</p><p><b>CONCLUSION</b>In elderly women with common malignant features on ultrasound, the thyroid nodules with a maximum diameter greater than 5 cm,anteroposterior-to-transverse diameter ratio less than 1,and microcalcifications are highly likely to be anaplastic thyroid carcinoma.</p>

Invasiveness of papillary thyroid microcarcinoma with BRAF mutation / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the invasiveness of papillary thyroid microcarcinoma(PTMC)with BRAF mutation.</p><p><b>METHODS</b>Totally 99 patients with PTMC with BRAF mutation were enrolled in this study, meanwhile another 97 patients with papillary thyroid carcinoma (PTC) (tumor size>1 cm)with BRAF mutation were included as controls. The clinicopathologic factors including extrathyroidal invasion, multifocality, and distant metastasis were analyzed.</p><p><b>RESULTS</b>The rates of extrathyroidal invasion and nodal metastasis in PTMC group were as high as 16.10% and 71.74%, respectively. In the PTMC group and PTC group,the extrathyroidal invasion rate was 16.10% and 39.18%, cervical lymph node metastasis rate was 71.74% and 91.75%, and distant metastasis rate was 1.01% and 9.28%, respectively. In the PTMC subgroups with tumor sizes ≤0.3 cm, 0.3-0.6 cm, and 0.6-1.0 cm, the cervical lymph node invasion rate was 60.00%, 72.50%, and 73.81%, the extrathyroidal invasion rate was 10.00%, 9.09%, and 24.44%, and the multifocality rate was 60.00%, 38.64%, and 57.78%, respectively. Univariate analysis showed that the tumor size was not significantly correlated with multifocality (Χ (2)=3.752, P=0.153), cervical lymph node metastasis (Χ (2) = 0.780,P = 0.677), extrathyroidal invasion (Χ (2) = 4.182, P = 0.124), and distant metastasis (Χ (2)=1.212, P = 0.545). While the BRAF group and PTC group were not significantly different in multifocality (Χ (2) = 1.742, P=0.187), they were significantly different in terms of extrathyroidal invasion (Χ (2) = 13.000, P = 0.000), nodal involvement (Χ (2) = 12.819, P = 0.000), and distant metastasis (Χ (2) = 5.316, P = 0.021). Multivariate analysis showed that nodal metastasis was independently associated with size>1 cm (P=0.001) and extrathyroidal invasion (P=0.003).</p><p><b>CONCLUSIONS</b>BRAF mutant PTMC manifests relative high extrathyroidal involvement and nodal metastasis, and the similar multifocality as BRAF mutant PTC. Radioactive iodine should be considered in PTMC with the presence of BRAF mutation combined with extrathyroidal invasion or nodal metastasis.</p>

Invasive properties of papillary thyroid cancer with concurrent BRAF(V600E) mutation and rearranged during transfection proto-oncogene protein expression / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the aggressive properties of papillary thyroid cancer (PTC) with concurrent BRAF(V600E) mutation and rearranged during transfection (RET) proto-oncogene protein expression.</p><p><b>METHODS</b>Fifty pathologically confirmed PTC patients who had received thyroidectomy were enrolled in this study. BRAF(V600E) mutation was detected by real time polymerase chain reaction (RT-PCR), while RET protein expression was measured by immunohistochemical SP method. Clinical and pathological features were compared between the concurrent BRAF(V600E) mutation and RET protein expression group (n=24) and BRAF(V600E) mutation or RET protein expression alone group (n=19). Seven patients were ruled out from the final analysis due to the absence of either BRAF(V600E) mutation or RET protein expression.</p><p><b>RESULTS</b>Of these 50 patients, BRAF(V600E) mutation and RET protein expression were detected in 38 patients (76%) and 28 patients (56%), respectively. Concurrent BRAF(V600E) mutation and RET expression was detected in 24 patients (48%). Compared with the concurrent BRAF(V600E) mutation and RET protein expression group, the BRAF(V600E) mutation or RET protein expression alone group had relatively poorer tissue differentiation and higher prognostic score (P=0.011, P=0.022).</p><p><b>CONCLUSION</b>PTC patients with concurrent BRAF(V600E) mutation and RET expression present poorer differentiation, more highly aggressive variant in carcinoma tissues, and higher cancer-related mortality risk.</p>

Invasive capacity of differentiated thyroid carcinoma in pediatric and adolescent patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the invasion features of differentiated thyroid carcinoma (DTC) in pediatric and adolescent patients.</p><p><b>METHODS</b>The clinical data of 32 DTC cases (≤18 years old) were retrospectively analyzed for the invasive capacity of DTC in terms of age and gender.</p><p><b>RESULTS</b>Bilateral (P=0.023), multifoci (P=0.037), and extrathyroid invasions (P=0.041) were more often in patients younger than 12 years old.</p><p><b>CONCLUSION</b>DTC in pediatric and adolescent patients tend to have a more aggressive pattern, especially in patients younger than 12 years.</p>

BRAF(V600E) mutation is not a positive predictor for distant metastasis in sporadic papillary thyroid carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>BRAF(V600E) mutation is correlated with local aggressive clinicopathological features in papillary thyroid carcinoma; yet the relationship between this genetic variation and distant papillary thyroid carcinoma metastasis was unclear. This study aimed to investigate whether BRAF(V600E) is predictive for distant metastasis in the Chinese population.</p><p><b>METHODS</b>One hundred and seven patients with papillary thyroid carcinoma were enrolled in this study, including 43 patients with distant metastasis and 64 patients without. Quantitative real-time polymerase chain reaction was used to detect BRAF(V600E) mutation, while immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF) expression. The associations between distant metastasis and BRAF(V600E) mutation, and VEGF expression as well as local clinicopathological factors were determined.</p><p><b>RESULTS</b>A total of 28.6% of the patients in the distant metastasis group harbored BRAF(V600E) mutation, which was significantly lower than in the without distant metastasis group (68.8%, P < 0.001). BRAF(V600E) mutation was negatively correlated with positive VEGF expression (P = 0.001). Furthermore, 52.2% of the patients with distant metastasis exhibited VEGF expression, compared with 25.0% of those without. Higher levels of VEGF expression were also observed in the distant metastasis group. Tumor size, extra-thyroid invasion, and BRAF(V600E) mutation were independent predictors for distant metastasis according to multivariate analysis (odds ratios were 2.8, 12.4, and 0.3; 95% CI 1.483-5.334, and 2.950-52.407, 0.100-0.890; P = 0.002, 0.001, and 0.030, respectively). BRAF(V600E) mutation was negatively correlated with distant metastasis in adult subgroup analysis (P = 0.005) but was not an independent parameter.</p><p><b>CONCLUSIONS</b>BRAF(V600E) mutation is predictive for distant metastasis in papillary thyroid carcinoma but not positively. VEGF may be involved in the pathogenesis of distant metastasis.</p>

Comparative study between primary mediastinal B-cell lymphoma and non-mediastinal diffuse large B-cell lymphoma by immunoglobulin gene rearrangement and Epstein-Barr virus infection detection / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the differences between primary mediastinal B-cell lymphoma (PMBCL) and non-mediastinal conventional diffuse large B-cell common lymphoma (DLBCL) in immunoglobulin gene rearrangement and EB virus infections.</p><p><b>METHODS</b>Twenty cases of PMBCL and 30 cases of non-mediastinal DLBCL were collected from September, 2000 to May, 2011. Pathological data were retrospectively analysed. Immunoglobulin heavy chain and light chain gene rearrangements and EBER in-situ hybridization were performed.</p><p><b>RESULTS</b>Six of 20 cases of PMBCL showed monoclonal gene rearrangement, all of which were weakly detected. Twenty-seven of 30 cases of ordinary diffuse large B-cell lymphoma showed monoclonal gene rearrangement, which were strongly detected (90.0%). Only 1 of 20 cases PMBCL and 2 of 30 cases of DLBCL were positive for EBER in-situ hybridization.</p><p><b>CONCLUSIONS</b>The detection rate of immunoglobulin gene rearrangement is significantly lower in PMBCL than that of non-mediastinal DLBCL. However, EB virus infection rates are very low in both types of lymphomas.</p>

Correlation between KRAS mutations and clinicopathologic features in colorectal carcinomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate mutations of KRAS gene and clinicopathological characteristics of colorectal carcinomas (CRC) in Chinese.</p><p><b>METHODS</b>Tumor cells were collected by microdissection from paraffin-embedded tumor specimens and adjacent normal colon tissues from 167 CRC patients. Genomic DNA was extracted and mutations of KRAS gene (codons 12 and 13) were detected by scorpions amplification refractory mutation system (Scorpions ARMS).</p><p><b>RESULTS</b>KRAS mutations were identified in 66 patients (39.5%), including G13D (21 cases, 12.6%), G12D (15 cases, 9.0%), G12V (13 cases, 7.8%), G12C (6 cases, 3.6%), G12A (5 cases, 3.0%), G12S (4 cases, 2.4%) and G12R (2 cases, 1.2%). Female patients had a higher KRAS mutation rate than male (50.0%, 29/58 vs.33.9%, 37/109, P < 0.05). However, KRAS mutations did not correlate with the patient age, tumor sites, histological types and grades (P > 0.05). Additionally, 7 of 18 patients with metastatic CRC had KRAS gene mutations. Overall, KRAS gene mutation was identified in 59 patients among 149 primary CRC (39.6%). There was no significant difference in KRAS mutation between primary and metastatic tumors (P > 0.05).</p><p><b>CONCLUSIONS</b>The detection rate of KRAS mutation is higher in female CRC patients than the males. The presence of KRAS mutation does not significantly correlate with the patients' age, tumor site, differentiation grades and histological types. There was no significant difference in KRAS mutation between the primary and metastatic tumors.</p>

Relationship between EGFR and KRAS mutations and prognosis in Chinese patients with non-small cell lung cancer: a mutation analysis with real-time polymerase chain reaction using scorpion amplification refractory mutation system / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC), and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency.</p><p><b>METHODS</b>EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010, and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study.</p><p><b>RESULTS</b>EGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC, in which three types of EGFR gene mutations were found: deletion in exon 19, exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations. There were 29(24.2%) patients with EGFR exon 19 deletion, 14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients. All the mutations were single point mutations, and no multiple points mutations detected. EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma (P = 0.009). EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P = 0.014, P = 0.001, respectively) in NSCLC patients. EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P = 0.008, P = 0.018, respectively). There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients. Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients. There were four types of KRAS gene mutations detected: KRAS Gly12Ala (GGT > GCT), KRAS Gly12Arg (GGT > CGT), KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT). There were 4 patients with Cys mutation, 2 with Arg mutation, 2 with Val mutation and 1 with multiple points mutation of both Cys and Arg in exon 12. No relationship was found between KRAS mutation and clinicopathological feature either in NSCLC or in adenocarcinoma. Prognosis was worse in patients with KRAS mutation than in wild-type patients (P = 0.008). No patient with both EGFR and KRAS mutation was detected.</p><p><b>CONCLUSIONS</b>EGFR mutation rate is related with gender, smoking history and pathological type in NSCLC patients, and is also related with differentiation and smoking history in adenocarcinoma patients. And prognosis is worse in patients with KRAS mutation than that with wild type.</p>

Tubulolobular carcinoma of breast: a clinicopathologic study of 8 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC).</p><p><b>METHODS</b>Eight cases of TLC were retrieved from 97 cases of invasive lobular carcinoma between January 2005 and March 2010 in the Peking Union Medical College Hospital. The clinical features and pathologic findings were studied and immunohistochemistry was performed for the expression of ER, PR, HER2, p53, E-cadherin, CK34βE12 and CK8.</p><p><b>RESULTS</b>Among the breast cancer patients, the incidence of TLC was about 1.0% (8/880). The mean age of the patients was 59 years, with a range of 45 to 79 years. All patients were asymptomatic, with incidental finding of a mass in the breast on health examination. Common findings on sonography included a hypoechoic nodule with irregular shape and spiculated margin. Histologically, the small uniform tumor cells were arranged in a mixed pattern showing single cells, single-cell files or cords, small round to angulated tubules, and infiltrating lobular or targetoid patterns around ducts that were specific for classical invasive lobular carcinoma. Low or intermediate grade intraepithelial neoplasms which had similar cellular morphology with the invasive tumor often appeared in the periphery, including ductal carcinoma in situ, lobular carcinoma in situ and intraductal papillary carcinoma. Immunohistochemistry of the tumor cells showed intense reactivity to ER (7/8) and PR (8/8), but no reactivity to HER2 or p53. Both the tubules and single-cell file or cords expressed E-cadherin (7/8), CK34βE12 (5/8), and CK8 (8/8) with a uniform staining pattern. All patients underwent modified radical mastectomy and 2/8 patients had metastatic carcinoma in the axillary lymph nodes. Seven patients were followed up for 28 to 75 months and remained well, including one patient that had a new breast mass 60 months after surgery, but had no treatment up to now.</p><p><b>CONCLUSIONS</b>TLC is a rare variant of invasive breast cancer and reveals mixed histologic features of both tubular and lobular carcinoma with common expression of E-cadherin, CK8 and CK34βE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.</p>

Clinicopathologic features and expression of epidermal growth factor receptor and vascular endothelial growth factor in adrenocortical tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in adrenocortical tumors.</p><p><b>METHODS</b>Forty-two cases of adrenocortical tumors operated at the Beijing Union Medical College Hospital during the period from July, 2001 to July, 2010 were retrospectively reviewed. Immunohistochemical study for EGFR and VEGF was carried out. The clinical information and follow-up data were analyzed.</p><p><b>RESULTS</b>The cases included 21 adrenocortical carcinomas (ACC) and 21 adrenocortical adenomas (ACA). Nine patients suffered from primary aldosterone syndrome, including 8 cases with ACA and 1 case with ACC. The average tumor size, tumor weight, and duration between disease onset and diagnosis in the 21 cases of ACC were 11.7 cm, 542 g and 8.5 months, respectively. This was in contrast to 3 cm, 9.8 g and 45.6 months, respectively in cases of ACA. Histologically, the WEISS score in all the 21 cases of ACA was ≤ 2 (average = 0.9). None of the ACC cases had score less than 4 (average = 6.6). The presence of sinus invasion correlated with tumor metastasis (P < 0.01). Immunohistochemical study showed that EGFR was expressed in 61.9% of ACC patients (13/21), whereas EGFR staining was mostly negative in ACA (except for weak staining in 5 cases and moderate staining in 1 case). The difference of EGFR expression between ACC and ACA was statistically significant (P = 0.030). On the other hand, the positive rate of VEGF in ACC was 71.4% (15/21), including 28.6% (6/21) with strong expression and 28.6% (6/21) with moderate expression. In contrast, the expression rate of VEGF in ACA was 30.0% (7/21), including 14.3% (3/21) with moderate expression. The difference of VEGF expression between ACC and ACA was statistically significant (P = 0.013). There was correlation between VEGF expression and venous invasion (P = 0.028). The average duration of survival in patients with ACC was shorter than that in ACA. The tumor weight in ACC also correlated with prognosis.</p><p><b>CONCLUSIONS</b>Tumor size, weight and presence of endocrine symptoms may help in the differential diagnosis between ACC and ACA. A WEISS score of ≥ 3 highly suggests ACC. The presence of sinus invasion is associated with metastasis. EGFR or VEGF expression may also be important in differentiating ACC from ACA.</p>

Diffuse pulmonary metastases with negative ¹⁸FDG positron emission tomography/computed tomography and positive post-radioiodine therapy scan of papillary thyroid cancer / 中华医学杂志(英文版)

A female papillary thyroid cancer patient with diffuse micronodular pulmonary metastases was confirmed only by post radioactive iodine (RAI) therapy whole body scan (RxWBS). Her diagnostic iodine-131 whole body scan (DxWBS), chest CT and 18FDG PET/CT scan were all negative. Attention and pitfalls of this case concerning surgical and RAI dose management are against current international guidelines on thyroid cancer.

Pure mucinous carcinoma of the breast: a clinicopathologic analysis with 56 patients / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To assess recent trends and prognostic features in the treatment of pure mucinous carcinoma (PMC) of the breast.</p><p><b>METHODS</b>Fifty-six patients diagnosed with PMC of the breast in our hospital from December 1982 to June 2008 were included. We evaluated the general information and tumor characteristics of the patients, examined the relationship between these factors and prognosis. Fisher's exact test was applied to analyze tumor characteristics.</p><p><b>RESULTS</b>The mean age of the patients was 53.7 years. The majority of the patients presented with early stage disease. Tumor size was found not a significant prognostic factor in this study. Mean follow-up period was 39 months and no breast cancer-related deaths were identified in the patient cohort.</p><p><b>CONCLUSIONS</b>PMC of the breast has a favorable prognosis. Tumor size does not appear to significantly impact survival.</p>

Analysis of chromosomal abnormalities in pancreatic cancer by spectral karyotyping / 中华病理学杂志

<p><b>OBJECTIVE</b>to investigate the chromosomal characteristics of pancreatic ductal adenocarcinomas by spectral karyotyping.</p><p><b>METHODS</b>cytogenetic aberrations of pancreatic cancer cell line P2 established from a Chinese patient was investigated by spectral karyotyping (SKY). Chromosomal alterations were further evaluated in 10 cases of pancreatic cancer and 10 cases of chronic pancreatitis by two color fluorescence in situ hybridization (FISH) by using EGFR/CEP7 probe and paraffin embedded tissue samples.</p><p><b>RESULTS</b>hypotriploid and 26 chromosomal aberrations were revealed in cell line P2. Recurrent chromosomal numerical alterations included loss of chromosome 4, 9, 18, 19, 22, Y, 10p, 15p, 8p, 6q and 12p, with gain of chromosome 7 and 12q. Frequent chromosomal structural abnormalities included der(9;15)(q10;q10), der(10)(3;10)(?;q26) and der(12)(8;12)(?;p13). Four of 10 cases showed EGFR copy number changes by FISH.</p><p><b>CONCLUSIONS</b>highly complex chromosomal rearrangements occur in pancreatic cancers. Additional studies of more cases are needed, including FISH analysis of EGFR copy number changes, to reach a conclusion.</p>

Morphological diagnosis of endometrial intraepithelial neoplasia and expression of PTEN / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic applications of endometrial intraepithelial neoplasia (EIN), and the expression of PTEN in endometrial lesions.</p><p><b>METHODS</b>Fifty-one cases of endometrial lesions were enrolled in this study. Using diagnostic criteria of EIN, the diagnosis were made and compared with the original results. Immunohistochemistry for PTEN was performed in all cases.</p><p><b>RESULTS</b>Two cases of simple hyperplasia originally diagnosed were reclassified as EIN. Three cases with atypia originally diagnosed showed no EIN pattern. PTEN deletion rates were 50.0%, 50.0%, 66.7% and 81.8% in proliferative endometrium, benign hyperplasia, EIN and endometrial carcinoma, respectively.</p><p><b>CONCLUSIONS</b>Diagnosis of EIN is applicable and its morphology and diagnostic criteria are different from the classical one (WHO94) for endometrial hyperplasia. Detection of PTEN deletion by immunohistochemistry is useful in identifying EIN, but cannot be used as an ultimate confirming factor.</p>

Pulmonary adenocarcinoma with micropapillary pattern: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics and immunohistochemical profile of lung adenocarcinomas with a micropapillary pattern (MPP).</p><p><b>METHODS</b>Among 135 cases of lung adenocarcinomas, the clinical, histological and immunohistochemical features of 48 cases of lung adenocarcinomas with a micropapillary components (the micropapillary components > or = 10%) were studied. The literature was reviewed.</p><p><b>RESULTS</b>All the 135 cases were resected pulmonary adenocarcinomas. Among 48 cases of lung adenocarcinomas with a micropapillary components, the age of patients ranged from 43 to 85 years (mean = 60.7 years). The male-to-female ratio was 9:7. Histologically, 36 cases of lung adenocarcinomas with the MPP were characterized by small papillary tufts lacking a central fibrovascular core lying freely within alveolar spaces (IA type) or in the clefts of fibrous tissue just like those in MPP breast cancers (IB type). Another type of the micropapillary pattern consisted of 12 cases, the micropapillary tufts floating within cystic spaces lined by tumor cells (II type). In micropapillary pattern-positive cases, lymphatic invasion and lymph node metastasis were identified significantly more frequently than in micropapillary pattern-negative cases (P < 0.01). The percentages of cases positive for various markers were 97.9% (47/48) for E-cadherin, 89.5% (43/48) for beta-catenin, 91.7% (44/48) for Muc-1, 70.8% (34/48) for epidermal growth factor receptor, 35.4% (17/48) for p53, 93.8% (45/48) for Ki-67. The percentages of cases with high expression (including 3+ or 4+) for these markers were 72.3% (34/47) for E-cadherin, 90.7% (39/43) for beta-catenin, 88.6% (39/44) for Muc-1, 52.8% (19/36) for epidermal growth factor receptor, 58.8% (10/17) for p53, 46.7% (16/36) for Ki-67. Adequate clinical follow-up information was available for 36 patients. The mean follow-up time was 21.1 months. Among these, 16 of 36 patients (44.4%) were alive with no evidence of tumor, 12(33.3%) were died, and 8 (22.2%) were alive with tumor.</p><p><b>CONCLUSION</b>Lung adenocarcinomas with the MPP correlates positively with lymphatic invasion and lymph node metastasis, and are likely to have a potential for high malignancy, suggesting a poor prognosis.</p>

Detection of epidermal growth factor receptor gene mutations in non-small cell lung cancers by real-time polymerase chain reaction using scorpion amplification refractory mutation system / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate mutations of EGFR gene in non-small cell lung cancers (NSCLC) using scorpions amplification refractory mutation system (Scorpions ARMS) is in comparing the detection sensitivity with that by PCR-direct sequencing method, and in addition to study the correlation between the mutations and the clinicopathological characteristics of the patients.</p><p><b>METHODS</b>Tumor cells were collected by microdissection from paraffin embedded tumor specimens and adjacent normal lung tissues of 82 NSCLC patients. The genomic DNA was extracted. Mutations of EGFR gene (exons 18, 19, 20 and 21) were detected by PCR-direct sequencing and Scorpions ARMS methods respectively.</p><p><b>RESULTS</b>Somatic mutations were identified involving the tyrosine kinase domain of the EGFR gene in 42 of 82 cases with a mutation detection rate of 51.2% by Scorpions ARMS assay. In-frame deletions of exon 19 occurred in 20 patients and point mutation occurred at codon 858, 861 (exon 21) in 18 and 1 patients respectively. Two patients had insertions mutations and 1 patient had point mutation occurring at codon 768 (exon 20). Among the 58 informative cases analyzed by PCR-direct sequencing, 25 mutations (detection rate of 30.5%) were identified. In-frame deletions of exon 19 occurred in 13 patients and point mutation occurred at codon 858, 861 (exon 21) in 10 and 1 patients respectively. In addition, 1 patient had point mutation at codon 768 (exon 20). Overall, Scorpions ARMS assay was more sensitive in detecting mutations of EGFR than PCR-direct sequencing.</p><p><b>CONCLUSIONS</b>A higher incidence of somatic mutations of EGFR gene was detected in NSCLC of Chinese patients. Mutations were more common in female, non-smoking patients with adenocarcinoma and bronchioloalveolar carcinoma histology. Scorpions ARMS method is quicker, more sensitive and accurate in detecting the EGFR gene mutations and should provide important therapeutic and prognostic information to the clinicians.</p>