Retroperitoneal seminoma in limited biopsies: morphologic criteria and immunohistochemical findings in 30 cases

The incidence of retroperitoneal seminoma is much less than that of its gonadal counterpart. Accurate diagnosis of retroperitoneal seminoma is critical, because it carries an excellent prognosis due to its favorable response to radiation therapy and/or cisplatin-based chemotherapy. However, correctly diagnosing a retroperitoneal seminoma may be challenging, especially when the biopsy material is limited. The present study was conducted to evaluate histologic findings and immunohistochemical staining patterns in biopsy specimens of retroperitoneal seminoma and to compare their utility as diagnostic tools. Thirty biopsy specimens of retroperitoneal seminoma were assessed for histologic characteristics and immunohistochemical expression of OCT4, c-kit, placental-like alkaline phosphatase, and cytokeratin AE1/AE3. The clinical information, morphologic features, and staining intensities and the percentages of positively staining tumor cells were analyzed. The mean age of patients was 38 years. Lymphocytic infiltration and nucleolar prominence in tumor cells were found in all 30 cases (100%). The incidence of other histologic characteristics were as follows: fibrous septa/stroma in 80% (24 cases), clear tumor cell cytoplasm in 70% (21 cases), tumor necrosis in 60% (18 cases), cellular pleomorphism in 53% (16 cases), granulomatous inflammation in 50% (15 cases), distinct cell borders in 46% (14 cases), intercellular edema in 23% (7 cases), and syncytiotrophoblasts in 3% (1 case). The mean mitotic count was 3 (range 0 to 15) per 10 high-power fields. All 30 cases (100%) of retroperitoneal seminoma revealed moderate to strong nuclear OCT4 staining in more than 50% of tumor cells. Twenty-one cases (70%) showed membranous expression of c-kit by tumor cells, with moderate to strong staining intensity in most cases. Variable degrees of staining for placental-like alkaline phosphatase were identified in 23 cases (77%) with occasional background staining artifact. Six cases (20%) displayed a positive cytokeratin AE1/AE3 staining pattern with weak to moderate intensity. In conclusion, the most common histologic findings in limited biopsy specimens of retroperitoneal seminoma were lymphocytic infiltration and nucleolar prominence in tumor cell nuclei. OCT4 immunostaining, with its superior sensitivity and easy interpretation compared with other markers, is a powerful tool for confirming the diagnosis of retroperitoneal seminoma.     

p16INK4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia

It has been repeatedly shown that there is a substantial lack of interobserver reproducibility in the histologic diagnosis of cervical intraepithelial neoplasia (CIN), which might be improved by a more specific diagnostic biomarker. Cervical cancer and CIN, but not other cervical epithelia, express high levels of the cyclin-dependent kinase inhibitor p16, suggesting that staining for this marker could help to more precisely identify CIN in tissue sections and therefore reduce variation in interpretation of cervical lesions. To test this hypothesis, 194 cervical cone biopsy samples were selected from a routine histopathology laboratory. Two consecutive sections from each biopsy were stained with hematoxylin and eosin and with a p16 -specific monoclonal antibody, respectively. Five experienced cervical pathologists examined the slides. The agreement in the diagnosis between pairs or groups of observers was calculated by kappa statistics. Significant discrepancies were observed in the diagnostic interpretation of hematoxylin and eosin-stained slides, particularly for low-grade lesions (kappa value 0.60 [95% confidence interval 0.58-0.63]). There was significantly better agreement in the interpretation of p16 expression (kappa value 0.91 [95% confidence interval 0.84-0.99]). Expression of p16 was restricted to CIN 2/CIN 3, CIN 1 associated with high-risk human papillomavirus, or cervical cancer. p16 immunostaining allowed precise identification of even small CIN or cervical cancer lesions in biopsy sections and helped to reduce interobserver variation in the histopathologic interpretation of cervical biopsy specimens. Thus, p16 immunohistochemistry can reduce false-negative and false-positive biopsy interpretation and thereby significantly improve cervical (pre)-cancer diagnosis.     

The presence of micropapillary features and retraction artifact in core needle biopsy material predicts lymph node metastasis in breast carcinoma

Retraction artifact around tumor cell nests is a characteristic feature of invasive micropapillary carcinoma (IMPC), a special type of breast cancer commonly associated with nodal metastasis. We have recently reported that the extent of retraction artifact in usual invasive ductal carcinomas (IDC) is also a strong predictor of nodal metastasis. We examined whether the presence and extent of micropapillary features and retraction artifact in core needle biopsy of breast cancers can predict nodal metastasis in a prospective series of 47 IMPC and 424 IDC. Micropapillary features were present on core needle biopsy in 28 of 47 IMPC cases. Nodal metastases were found in 21 of 28 and 14 of 19 IMPC cases with and without micropapillary features present on core needle biopsy, respectively. Lymph node metastasis was significantly associated with the presence of micropapillary features, but not with its extent within these tumors. The presence of extensive retraction artifact in core needle biopsy samples of IDC also showed a significant association with nodal metastasis. Our results indicate that the presence of micropapillary features or extensive retraction artifact on core needle biopsy of breast carcinoma can predict nodal metastasis. Our results support the notion that the characteristic clear spaces separating the tumor cells from the stroma in IMPC and IDC of the breast are not a random artifactual phenomenon simply resulting from tissue fixation and processing, but rather they are likely related to altered tumor-stromal interactions, which might have an important role in lymphatic tumor spread.     

Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma

Retraction artifact resulting in clear spaces around tumor cell nests is frequently seen in histologic material and may present difficulty in their differentiation from lymphovascular invasion. We noticed that retraction artifact seemed to be more common around groups of breast cancer cells compared with benign acini, and when extensively present, metastasis to axillary lymph nodes was often seen. Thus, we performed a study of 304 cases of stage pT1 and pT2 breast carcinomas to test our hypothesis that extensive retraction artifact in tumors correlates with lymphatic spread and outcome. Tumors were evaluated to determine the presence and extent of retraction artifact around tumor cell nests and the presence of lymphatic invasion. Lymphatic invasion was confirmed by D2-40 immunostaining. The extent of retraction artifact in tumors was correlated with clinicopathologic tumor features and patient outcome. Variable degree of retraction artifact was present in 183 of 304 (60%) invasive carcinomas, with its extent ranging from 0% to 90% (median 5%). The extent of retraction artifact showed a significant correlation with tumor size, histologic type, histologic grade, presence of lymphovascular invasion, and nodal metastasis. Further, extensive retraction artifact was significantly associated with poor overall and disease-free survival in both univariate and multivariate analyses. We propose that the apparent retraction of the stroma from cells of invasive breast carcinoma on routine histologic sections is not a phenomenon merely due to inadequate fixation as currently believed. Rather, it likely signifies important biologic changes that alter tumor-stromal interactions and contribute to lymphatic spread and tumor progression.     

Management of noninvasive carcinoma of the cervix

The diagnosis of noninvasive cancer of the cervix depends on carefully performed pelvic examinations and accurate cytology. Their management is determined by the histologic picture of the lesion. Adequate biopsy material must rule out invasive cancer before conservative measures are adopted. Unless special facilities are available, a cone biopsy and D & C should be performed on all nonpregnant cases with punch biopsies showing severe dysplasia or carcinoma-in-situ. These entities are classified as CIN III according to the most modern classification. Cone biopsies and D & C should also be performed on cases with negative punch biopsies and suspicious cytology. Colposcopic diagnosis diagnosis and outpatient management of these lesions should be performed only in a clinic with the specialized facilities already outlined.     

Yield and efficacy of biopty gun testis needle biopsy

OBJECTIVES: To assess whether a preliminary skin incision enhances diagnostic yield of percutaneous testis biopsy and to further evaluate the clinical efficacy of this procedure. METHODS: A total of 45 men (67 testes) underwent testicular biopsy with two passes of a Biopty gun spring-loaded needle. Twenty-seven biopsies were performed without a preliminary skin incision (group 1), and 40 were performed after a small scrotal incision (group 2). In 56 testes, needle biopsy histopathologic diagnosis was compared with that of open biopsy or orchiectomy specimens from the same patient. Needle and surgical specimens were fixed in Bouin's solution and sent separately for independent, blinded, histologic interpretation. RESULTS: Complications of the procedure were negligible. In all 67 needle biopsies, specimen quality was adequate for histopathologic interpretation. The mean number of seminiferous tubules obtained from needle biopsy was 28% higher among patients having a preliminary skin incision (25.9) compared with those without (18.7, P = 0.023). Correlation between needle and open histopathologic diagnosis was excellent (55 of 56, 98%). CONCLUSIONS: A preliminary skin incision made before needle biopsy increases the diagnostic yield of percutaneous testis biopsy. Percutaneous testis biopsy using the Biopty gun needle provides equal diagnostic information when compared with open testis biopsy or orchiectomy specimens. The concomitant reduction in morbidity and cost make this an attractive diagnostic procedure.     

Interpretation of endomyocardial biopsy after heart transplantation. Potentially confusing factors

Histological examination of the myocardium by endomyocardial biopsy is a standard method of monitoring the presence of acute rejection in the transplanted heart. The histopathological consequences of the biopsy procedure itself have been investigated in non-transplanted hearts in the baboon. Organization of thrombus, necrosis of myocytes adjacent to the biopsy site, and mononuclear cells (including T lymphocytes) surrounding the biopsy site appear after biopsy; should a subsequent biopsy be taken from this area, these appearances may be confused with the appearances associated with acute or resolving cardiac rejection. This problem has been encountered in the clinical transplant programme. Observations on the myocardial histopathological changes resulting from brain death and from parasitic infestation, both of which may also lead to confusion in the interpretation of endomyocardial biopsies, are also presented. Awareness of these factors in patients with heart transplants should lead to caution in the interpretation of the histopathological features and may avoid unnecessary extra immunosuppression early after transplantation. Observations indicate that endomyocardial biopsy should not be the sole method of monitoring for the development of acute rejection.     

Aspiration biopsy of prostate

Needle biopsy of the prostate has been widely practiced for more than twenty-five years, whereas transrectal aspiration biopsy, first described fifty years ago, has not. We describe our experience using the transrectal aspiration biopsy and correlate the results with histologic studies of the prostate obtained by conventional needle biopsy and surgical specimens. Aspiration needle biopsy of the prostate has a high degree of diagnostic accuracy, it causes minimal inconvenience and discomfort, the results are rapidly available, the ease of entering the suspected area in the prostate is more precise than with conventional needle biopsy, and sampling of prostate can be greater. The disadvantages of aspiration biopsy are that the technique, being unfamiliar to most urologists, must be learned and requires an experienced cytologist for interpretation. Cytologic evaluation by aspiration biopsy and the histologic diagnosis by conventional needle biopsy are complementary.     

Significance of denuded urothelium in papillary urothelial lesions

Flat urothelial carcinoma in situ (CIS) is often characterized by prominent dyscohesion with some cases having only a few clinging CIS cells remaining on biopsy. The finding of extensive denudation on urothelial biopsies is associated with a risk of CIS on either prior or subsequent biopsies. The significance of denudation in papillary urothelial lesions has not been formally studied. We identified from our surgical pathology files 31 specimens (from 28 patients) of papillary urothelial lesions with extensive denudation. In cases in which denudation was associated with low-grade urothelial neoplasms, follow-up of subsequent cytologic and histologic specimens was obtained. Of the 28 patients, 25 (89%) were men and 3 (11%) were women with an age range of 40 to 88 years old (mean age 62). Of 31 biopsies, 15 were from anatomically confined areas (ie, renal pelvis, ureter, and urethra). In 22/28 (79%) patients, prominent denudation was associated with high-grade papillary carcinomas, 4/28 (14%) low-grade papillary carcinomas, and 2/28 (7%) papillary urothelial neoplasms of low-grade malignant potential. The average extent of urothelial denudation was 82% with 61% of cases having > or =90% denudation. Prominent cautery artifact was present in 17/31 (55%) cases. In 13/28 patients with high-grade lesions, there was a concurrent biopsy of a second urothelial lesion that was either high-grade papillary urothelial carcinoma or invasive urothelial carcinoma. Five of the 6 patients in which the prominent denudation was associated with a low-grade papillary urothelial lesion have not progressed to a high-grade lesion. One patient with a denuded papillary urothelial neoplasm of low malignant neoplasm was subsequently diagnosed with a noninvasive low-grade papillary urothelial carcinoma in the bladder and a high-grade infiltrating urothelial carcinoma of the ureter. We conclude that (1) the majority of papillary urothelial lesions associated with prominent urothelial denudation are high grade; (2) a significant percentage of papillary urothelial lesions with denudation occur with either prominent cautery artifact or in anatomically confined areas, suggesting both iatrogenic and mechanical contributing factors, respectively; (3) a minority of cases with prominent urothelial denudation occur in association with low-grade papillary urothelial lesions and are not associated with progression to higher grade lesions on follow-up studies; and (4) prominent urothelial denudation in papillary lesions should prompt careful examination of these specimens for rare clinging high-grade carcinoma cells, although in a minority of cases the underlying lesion will be low grade.     

Does the Method of Biopsy Affect the Incidence of Sentinel Lymph Node Metastases?

More detailed examination of the sentinel lymph node (SLN) in breast cancer has raised concerns about the clinical significance of micrometastases, specifically isolated tumor cells detected only through immunohistochemical (IHC) staining. It has been suggested that these cells do not carry the same biologic implications as true metastatic foci and may represent artifact. A retrospective institutional review board-approved review was conducted on clinically node-negative breast cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003. Retrospective analysis of tumor characteristics and the method of the initial diagnostic biopsy were correlated with the presence and nature of metastatic disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E) positive. SLN positivity strongly correlated with tumor size (p<0.001) and tumor grade (p=0.025), but not with the method of biopsy (needle versus excisional biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC (n=381). Of the 291 H&E-negative patients, 26 had IHC-only detected micrometastases (9%). The likelihood of detecting IHC-only metastases did not correlate with tumor size or grade, but was significantly higher in patients undergoing excisional biopsy than core needle biopsy. While the method of biopsy has no demonstrable effect on the likelihood of finding metastases in the SLN by routine serial sectioning and H&E staining, it may significantly impact the likelihood of finding micrometastases by IHC. IHC should not be used routinely in the evaluation of the SLN and caution should be used when basing treatment decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC-only detected micrometastases.     

Reexcision perineural invasion. Not a sign of malignancy

Perineural invasion has been reported to occur in both benign and malignant neoplasms. We describe two cases in which perineural invasion by epithelial cells was present in reexcision skin specimens removed because of melanocytic lesions in the original biopsy material. Because of the absence of a primary epithelial neoplasm, this phenomenon was interpreted as a reactive or reparative process, most probably resulting from regenerating traumatized sweat gland ducts. On the basis of this study alone, it may not be possible to distinguish between reexcision perineural invasion and perineural invasion from a primary epithelial neoplasm. For such cases, the following histologic features serve as provisional guidelines favoring an interpretation of reexcision perineural invasion: absence of perineural spread beyond the immediate previous biopsy site, benign appearance of the perineural epithelial cells different from the appearance of the original tumor, and absence of residual epithelial tumor in the vicinity of the involved perineurium.     

Histologic heterogeneity of masses at percutaneous breast biopsy

The purpose of this study was to determine whether different histologic findings are obtained from different areas of breast masses seen on mammography when targeted on stereotactic breast biopsy. Twenty-one masses (mean size, 1.8 cm; range, 0.7–5.5 cm) underwent stereotactic biopsy using a 14-gauge directional vacuum-assisted biopsy probe (Mammotome, Biopsys/Ethicon Endo-Surgery, Cincinnati, OH). The central and peripheral areas of the mass were targeted and biopsied separately, and histologic findings from the targeted center and periphery were compared. Six of 21 masses (29%) were heterogeneous, yielding different histologic results from the targeted center and periphery. In 4 heterogeneous masses, which constituted 4 of 21 masses (19%) in this study, surgical biopsy was recommended on the basis of findings obtained from only the center ( n = 2) or the periphery ( n = 2). Stereotactic biopsy findings in these 4 masses were atypia in 3 and radial scar in 1; none of these 4 masses had carcinoma at surgery. In all 4 masses that proved to be malignant, the diagnosis of carcinoma was made in specimens obtained from both the targeted center and the periphery of the mass. Breast masses can be heterogeneous, yielding different histologic findings from different areas of the mass. Our data suggest that sampling part but not all of a mass may miss certain histologic components of the mass, but should not result in a failure to diagnose carcinoma.     

Fine-needle aspiration biopsy of pancreatic masses

The results of fine-needle aspiration biopsy of pancreatic masses in 79 patients (percutaneous with ultrasonic guidance in 23 and peroperative in 56) were evaluated and correlated to survival (follow-up at least 2 years). The original biopsy diagnosis was malignancy in 41 patients, histologically confirmed in 19, all but two of whom died of cancer within 18 months. None of the 22 patients without histologic verification of the primary malignant cytodiagnosis survived for 18 months. The fine-needle biopsy showed benign cells in 30 patients, in 13 of whom histologic diagnosis was obtained, revealing carcinoma in seven. Six of these seven died within a year, but of the six with histologically benign lesion, five survived for more than 2 years. All 17 patients without histologic verification of benign aspiration biopsy findings survived more than 24 months. The biopsy diagnosis was inconclusive in eight patients. Four of them proved to have carcinoma and died within 18 months. The sensitivity of fine-needle aspiration biopsy of the pancreas was 76% in this study and the predictive value for malignancy was 100%.     

The Differential Diagnosis of Acute Colitis: Clues to a Specific Diagnosis

This review describes a systematic approach to the interpretation of colonic biopsy specimens of patients with acute colitis. Five main histologic patterns are discussed: acute colitis, focal active colitis, pseudomembranous colitis, hemorrhagic colitis, and ischemic colitis. For each pattern, the most common etiologic associations and their differential diagnoses are presented. Strategies based on histologic analysis and clinical considerations to differentiate acute from chronic colitides are discussed.     

Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia

The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16INK4a, a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study, we assessed whether p16INK4a immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p16INK4a-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), kappa value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16INK4a-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16INK4a test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively), p16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia and may be a valuable aid for the interpretation of cervical histology.     

Improving results from nerve and muscle biopsy in children: technical considerations in the harvesting of specimens

The convergence of expertise in the neurological sciences, special interest in myoneuropathology, and improved surgical technique has resulted in a significantly improved yield from muscle and nerve biopsies in children with suspected neuromuscular disorders. We present a synthesis of all those factors that we have identified as contributing to optimal results, particularly site selection, sample size, a meticulous biopsy technique that avoids the introduction of artefacts, the use of the muscle biopsy clamp, prompt processing of the specimen, and participation of the neurologist in the biopsy procedure and the interpretation of the histologic sections.     

非对称性小RNA干扰技术介导的USP22基因沉默的研究

目的 观察非对称小干扰RNA(aiRNA)对膀胱癌EJ细胞泛素特异肽酶22(USP22)基因的沉默效率及特异性的影响.方法 设计并合成USP22基因的小干扰RNA(siRNA)及aiRNA,利用脂质体Translipid转染EJ细胞,采用实时荧光定量聚合酶链反应(PCR)检测转染前后EJ细胞USP22 mRNA的表达水平变化,比较USP22 siRNA与USP22 aiRNA对USP22基因沉默效率及特异性的差异.结果 浓度为50 nmol/L的15/21 USP22 aiRNA能明显抑制EJ细胞中USP22基因mRNA的表达,转染48 h后USP22 mRNA的表达水平下降到最低[(8.30±1.68)%,P＜0.05],且其沉默效率和特异性明显优于USP22 siRNA.结论 以非对称小RNA干扰技术为基础设计的USP22aiRNA能够有效沉默USP22基因,并且降低了非特异性的脱靶效应,减少了受RNA干扰中的"饱和机制"及"竞争机制"的影响,弥补了传统siRNA的一些不足.     

Evaluation of povidone abdominal washing for prevention of peritoneal cancer cell seeding: experimental study in the rat

GOAL: The aim of the study was to evaluate the in vitro cytototoxicity of diluted povidone iodine on colon cancer cells and its in vivo antitumoral effect in a model of peritoneal carcinomatosis in the rat. METHODS: Cell cytotoxicity of a povidone iodine diluted solution was assessed, in vitro, on rat colon cancer cells (DHD/K12/PROb) and human colon cancer cells (HT29). The antitumoral effect of diluted povidone iodine washing was measured in BDIX rats after the intraperitoneal inoculation of 10(6) DHD/K12/PROb cells. Results were compared to an abdominal washing within a 9 g/l salinel solution. In one experiment, peritoneal scars and a colocolic anastomosis were performed after the injection of cancer cells. RESULTS: A short 10 min incubation of human and rat colon cancer cells with diluted povidone iodine resulted in a complete cell killing. In animals, a peritoneal washing with 1% diluted povidone iodine completely inhibited the tumor growth in parietal peritoneum. However, development of peritoneal tumor nodules was not inhibited in the omentum, in scarified peritoneum or in intestinal anastomosis. CONCLUSIONS: Despite its high in vitro efficacy, diluted povidone iodine has an incomplete effect in the prevention of peritoneal carcinomatosis, with only a partial inhibition in scarred peritoneum epiplo?c area and intestinal anastomosis. In contrary, it procures a complete inhibition of tumor growth in normal peritoneum.     

泛素特异性肽酶22经Wnt/β-catenin通路调控结直肠癌化疗耐药的机制研究

目的探讨泛素特异性肽酶22（USP22）作用于Wnt/β-catenin信号通路参与结直肠癌的发生和化疗耐药的分子机制。 方法采用氟尿嘧啶（5-Fu）处理结直肠癌细胞株HT-29,建立耐药细胞株HT-29/5-Fu;构建USP22 siRNA稳定表达细胞株（表示为HT-29-sh USP22、HT-29/5-Fu-sh USP22）。CCK-8法检测HT-29/5-Fu细胞对5-Fu的敏感性、抑制USP22表达后结直肠癌细胞对5-Fu敏感性的影响;采用Western blotting检测不同质量浓度5-Fu诱导下HT-29细胞中USP22蛋白表达,HT-29和HT-29/5-Fu细胞中USP22和β-catenin蛋白表达,以及抑制USP22表达对结直肠癌细胞USP22、β-catenin表达的影响。 结果（1）HT-29与HT-29/5-Fu细胞对5-Fu的IC₅₀值分别为（1.58±0.23）mg/L和（14.58±0.94）mg/L,其中HT-29/5-Fu细胞对5-Fu的敏感性显著下降（n=6,t=8.476,P<0.01）。（2）在0.5、5.0 mg/L的5-Fu诱导后,HT-29细胞内USP22蛋白表达水平（USP22/β-actin）显著升高（0.5 mg/L vs 0 mg/L：t=7.618,P<0.05;5.0 mg/L vs 0 mg/L：t=6.992,P<0.05）。HT-29/5-Fu组中USP22蛋白表达水平为0.92±0.11,显著高于HT-29组的0.18±0.06（t=7.618,P<0.05）。（3）HT-29-sh USP22组对5-Fu的IC₅₀为（0.25±0.23）mg/L,显著低于HT-29组（t=6.662,P<0.01）。HT-29/5-Fu-sh USP22组对5-Fu的IC₅₀为（1.36±0.14）mg/L,显著低于HT-29/5-Fu组（t=7.002,P<0.01）,但与HT-29组相比,差异无统计学意义（t=1.586,P>0.05）,抑制USP22表达可增强结直肠癌细胞HT-29对5-Fu的敏感性。（4）HT-29-sh USP22组的USP22蛋白表达水平为0.07±0.01,与HT-29组相比下调（t=7.105,P<0.01）。HT-29/5-Fu-sh USP22组的USP22蛋白表达水平为0.33±0.02,与HT-29/5-Fu组相比,USP22蛋白表达水平下调（t=6.153,P<0.01）。HT-29-sh USP22、HT-29/5-Fu-sh USP22中β-catenin蛋白表达水平与相应对照组HT-29、HT-29/5-Fu相比显著下调（HT-29-sh USP22 vs HT-29：t=8.823,P<0.01;HT-29/5-Fu-sh USP22 vs HT-29/5-Fu：t=7.656,P<0.01）。 结论5-Fu可诱导结直肠癌细胞USP22表达增高。抑制USP22表达可增加结直肠癌细胞对5-Fu的药物敏感性,其机制可能是抑制Wnt/β-catenin信号通路,从而有效逆转结直肠癌细胞对5-Fu的耐药。     

The histology of interstitial cystitis

Several studies have reported histologic findings in interstitial cystitis (IC) bladder biopsy specimens. However, these studies used a variety of criteria to define IC, which may explain the variation noted in the histologic changes. Clinical experience shows that these biopsy specimens are often not helpful in confirming the diagnosis. Our study was designed to examine the histologic features identified in bladder biopsy specimens from patients with IC and compare them with biopsy specimens from a control population. Although IC patients as a group had a higher incidence and degree of denuded epithelium, ulceration, and submucosal inflammation, none of these findings was pathognomonic. In addition, these findings occurred only in interstitial cystitis patients with pyuria or small bladder capacity. The inflammatory infiltrate seen in IC was composed predominantly of lymphocytes, with increasing numbers of plasma cells as the degree of inflammation increased. There was no specific predilection for the inflammatory infiltrate to be perineural. Submucosal inflammation was associated with denuded epithelium, ulceration, pyuria, and a clinical response to therapy suggesting a pathophysiologic relationship. Epithelial and basement membrane thickness, submucosal edema, vascular ectasia, fibrosis, and detrusor muscle inflammation and fibrosis were not significantly different in the IC and control patients. These findings suggest that IC is a chronic submucosal inflammatory disease, at least in those patients with small bladder capacities or pyuria. IC is best diagnosed from its clinical features; the histologic changes identified in the bladder biopsy play a supportive role in this diagnosis. Mast cells play a limited role in the diagnosis of IC.