Cyclin D1 expression in oral squamous cell carcinoma and verrucous carcinoma: correlation with histological differentiation.

OBJECTIVE: To assess the expression of cyclin D1 in oral squamous cell carcinoma (OSCC) and verrucous carcinoma (VC), to compare its expression in both of these carcinomas, and to investigate the possible correlation of cyclin D1 expression in different histological grades of OSCC. STUDY DESIGN: Paraffin embedded tissues from 71 cases of OSCC and VC were studied immunohistochemically. Expression of protein was correlated between the 2 entities and in different grades of OSCC. RESULTS: Cyclin D1 overexpression was seen in 29 cases (70.7%) of OSCC and in 19 cases (63.3%) of verrucous carcinoma. Statistical significance at the 5% level was observed for cyclin D1 expression between all categories of squamous cell carcinoma (SCC), that is, between well-differentiated and moderately differentiated carcinomas, and between moderate and poorly differentiated carcinomas, and well and poorly differentiated squamous carcinomas. No statistical significance was observed in cyclin D1 expression between SCC and oral verrucous carcinoma; however, statistical significance was seen between oral VC and poorly differentiated squamous cell carcinoma. CONCLUSION: Increased expression of cyclin D1 significantly correlated with lack of differentiation in these malignant epithelial neoplasms.     

Immunohistochemical Coexpression of MUC1 and MUC4 in Oral Leukoplakia and Oral Squamous Cell Carcinoma

MUC1 and MUC4 are two transmembranous proteins, which have been seen to express aberrantly in various human neoplasms and advocated as independent prognostic markers. Till now no extensive studies have been carried out on combined expression of MUC1 and MUC4 in oral leukoplakia and Oral squamous cell carcinoma. This study is an endeavour to evaluate Immunohistochemical coexpression of MUC1 and MUC4 in Oral Leukoplakia and Oral squamous cell carcinoma and furthr establish them as prognostic markers. Immunohistochemical analysis of MUC1 and MUC4 was done on 24 cases of Oral squamous cell carcinoma, 24 cases of leukoplakia and 12 normal oral mucosal tissues. Chi square test and one way ANOVA test were employed for statistical analysis. Normal oral mucosa and leukoplakia group showed higher frequency of negative immunoexpression compared to oral squamous cell carcinoma group. Furthur in Oral squamous cell carcinoma group, higher frequency of double positive coexpression in well and moderately differentiated oral squamous cell carcinoma and single positive coexpression in poorly differentiated oral squamous cell carcinoma was obtained. A definite rise of immunoexpression of MUC1 and MUC4 was observed from normal oral mucosa to leukoplakia to oral squamous cell carcinoma indicative of their contribution as diagnostic and prognostic markers.Keyword: Immunohistochemistry, Coexpression, Leukoplakia, Oral squamous cell carcinoma     

三磷酸腺苷结合转运蛋白G超家族成员2基因在胃癌组织中的表达及意义

目的探讨三磷酸腺苷结合转运蛋白G超家族成员2（ABCG2）在胃癌组织中的表达及意义。方法采用免疫组织化学（免疫组化）方法（IHC染色）检测ABCG2在45例手术切除胃癌组织和30例正常胃黏膜中的表达情况：应用RT—PCR和实时定量PCR检测30例胃癌患者的癌组织及胃切缘正常胃黏膜ABCG2的mRNA表达。结果ABCG2在胃癌原发灶组织中有较高程度的表达．其阳性率为62．2％；而30例正常胃黏膜中的阳性表达率为6．7％；两者比较P〈0.05。ABCG2在低分化腺癌中的表达高于中-高分化腺癌（P〈0.05）；胃癌组织中ABCG2mRNA水平的表达明显高于胃正常黏膜（P〈0.05）．与免疫组化结果一致。结论ABCG2在胃癌组织中过度表达．其可能在某种程度上参与了胃癌的发生和发展，可以作为胃癌肿瘤干细胞研究的重要分子。     

Increased expression of the epidermal growth factor receptor on human colon carcinoma cells

Epidermal growth factor (EGF) is a small polypeptide hormone that promotes the growth of cells in culture and elicits the differentiation of epithelial tissues in vivo. The effect of EGF is mediated by a transmembrane receptor that is expressed in increased amounts on some tumor cells. We have used a monoclonal antibody to the EGF receptor to detect increased expression of the receptor on human colon carcinoma cells. All eight of the moderately well-differentiated colon carcinoma cell lines tested and several frozen colon carcinoma tissue sections showed increased expression of the EGF receptor, while five poorly differentiated colon carcinoma cell lines and normal colon tissue sections did not. Increased expression of the EGF receptor on moderately well-differentiated colon carcinoma cells but not on poorly differentiated colon carcinoma cells was also demonstrated by western transfer and iodine 125-labeled EGF binding assays. Increased expression of the EGF receptor on moderately well-differentiated colon carcinoma cells seems to be a useful marker for the differentiation of human colon carcinoma cells. In addition, it might provide a site for adjuvant hormonal therapy or immunotherapy.     

直肠癌全直肠系膜切除术系膜切缘微转移的临床研究

目的 对直肠癌患者系膜切缘微转移灶进行检测,研究其对局部复发的影响.方法 对52例Dukes A、B和C期直肠癌患者实施伞直肠系膜切除术,用RT-PCR技术检测系膜切缘组织细胞中角质蛋白CK20 mRNA.结果 本组52例直肠癌旁系膜中,21例CK20 mRNA呈阳性,31例为阴性,总阳性率为40%.Dukes A、B和C期阳性率分别为17%、30%和54%,直肠系膜切缘微转移发生率随肿瘤分期升高而增加,组间比较差异有统计学意义,P<0.05;高、中、低与未分化癌阳性表达率分别为43%、38%、40%和50%,病理分级之间CK20 mRNA表达阳性率差异无统计学意义(P>0.05).全组患者局部复发率为12%,CK20 mRNA阳性组和阴性组局部复发率分别为24%和3%,两组比较差异有统计学意义,P<0.05.结论 直肠系膜切缘微转移与局部复发有关,提示系膜CK20mRNA可能是一个潜在的局部复发标志物.     

Histologic differentiation and chemosensitivity of human head and neck squamous cell carcinomas

The chemosensitivities of 42 human head and neck squamous cell carcinomas were examined using the in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at surgery or biopsy were exposed to five different antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU), and 1-hexylcarbamoyl-5-fluorouracil (HCFU). The results were analyzed according to the histopathologic degree of differentiation of well, moderately, and poorly differentiated squamous cell carcinoma. The average decrease in succinate dehydrogenase activity was 43.2 +/- 24.9 for ADM, 29.0 +/- 14.2 for CDDP, 32.9 +/- 17.6 for CQ, 64.2 +/- 20.6 for 5-FU, and 26.8 +/- 16.9 for HCFU. There was a statistically significant difference in the decrease of succinate dehydrogenase activity between well and poorly differentiated squamous cell carcinomas. These data suggest that, for patients with a poorly differentiated squamous cell carcinoma, the response to anti-cancer drugs may be more satisfactory than in those with a well-differentiated squamous cell carcinoma.     

MCL-1在口腔鳞状细胞癌中的表达及意义

目的:探讨MCL-1在口腔鳞状细胞癌(Oral squamous cells carcinoma,OSCC)组织中的表达情况及意义。方法:采用免疫组织化学和实时荧光定量PCR技术,检测OSCC和口腔正常黏膜组织中MCL-1蛋白及mRNA的表达。结果:MCL-1蛋白在OSCC组织中的阳性表达率为61.9%(52/84),在口腔正常黏膜组织中的阳性表达率为15.0%(3/20),两组有显著性差异(P0.001);MCL-1 mRNA在OSCC肿瘤组织中的含量高于癌旁正常组织(P0.05)。结论:MCL-1的高表达在OSCC的发展过程中可能发挥了重要作用。     

结肠癌组织中Ku70和Sp1的表达变化及其意义

目的探讨Ku70和Sp1在结肠癌组织中的表达变化及其意义。方法选取2013年8月至2015年7月经病理检查确诊为结肠癌的患者79例,比较高、中、低分化结肠癌中Ku70蛋白和Sp1蛋白阳性表达率以及Ku70mRNA和Sp1mRNA相对表达量与癌旁组织的差异;统计分析用SPSS13.0软件进行,Ku70mRNA与Sp1mRNA相对表达量用均数±标准差表示,t检验进行两组比较;Ku70蛋白和Sp1蛋白阳性表达率用百分率(%)表示,χ2检验进行比较;Spearman相关和Pearson直线相关分别用于Ku70mRNA与Sp1mRNA相对表达量和Ku70蛋白和Sp1蛋白阳性表达率相关性分析;P0.05表示差异具有统计学意义。结果高、中、低分化结肠癌组织中Ku70阳性表达率分别为47.37%、61.54%、79.41%;Sp1蛋白阳性表达率分别为52.63%、76.92%、85.29%;结肠癌组织中Ku70、Sp1蛋白阳性表达率及mRNA水平均高于癌旁组织(χ2=29.792、50.009;P0.001);低分化结肠癌的Ku70、Sp1蛋白阳性表达率及mRNA水平显著的高于高分化结肠癌(F=29.084、39.167;P0.001)差异均有统计学意义;经过Spearman相关分析发现,Ku70蛋白与Sp1蛋白阳性表达率呈正相关,且差异具有统计学意义(r=0.307,P=0.006)。经过Pearson相关分析发现,Ku70mRNA相对表达量与Sp1mRNA相对表达量呈正相关,且差异具有统计学意义(r=0.458,P0.001)。结论结肠癌组织中Ku70和Sp1蛋白阳性表达率高于正常组织,且Ku70蛋白与Sp1蛋白阳性表达率以及Ku70mRNA与Sp1mRNA相对表达量呈正相关。     

Value of grading squamous cell carcinoma of the head and neck.

We report a series of 3,294 patients with squamous cell carcinoma of the head and neck seen by one of us between 1963 and 1990. Two thousand and seven patients had a histologically proven and graded, but previously untreated, squamous cell carcinoma of the mucosal surfaces of the head and neck. These tumors had been graded previously by many different pathologists in many different hospitals, both in the United Kingdom and the United States, as well as continental Europe, over this period. Of the host factors both sex and age were associated with differentiation: 34% of patients less than age 50 had a well-differentiated tumor compared with 44% greater than age 50; 32% of women had a poorly differentiated tumor compared with 26% of men. General condition had no correlation with degree of differentiation. Site was closely associated with grading: well-differentiated tumors were more common in the mouth and larynx and poorly differentiated tumors in the pharynx. Furthermore, of poorly differentiated tumors, 19% arose from areas normally lined by keratinized squamous epithelium, 22% from a nonkeratinized area, 36% from respiratory epithelium, and 45% from areas normally covered by lymphoid epithelium. T stage had no significant correlation with differentiation. However, 46% of patients with poorly differentiated tumors had a nodal metastasis at presentation compared with only 28% of well-differentiated tumors. Distant metastases at presentation were found in 3.4% of poorly differentiated tumors compared with 1.8% of well-differentiated tumors. The survival fell significantly from 33% for well-differentiated tumors to 27% for poorly differentiated tumors. The recurrence rate at the primary site rose from 25% for well-differentiated tumors to 27% for poorly differentiated tumors, and recurrence in the lymph nodes rose from 26% to 30%. Both differences were just significant.     

CD44 Expression in Intraoral Salivary Ductal Papillomas and Oral Papillary Squamous Cell Carcinoma

CD44 is a transmembrane adhesion molecule which has been previously shown to be useful in the differentiation of benign papillary lesions from invasive carcinoma in several different areas including sinonasal mucosa and breast tissue. CD44 expression has previously been shown to be lost in invasive carcinoma and retained in benign papillary lesions in both of the above locations. In addition, studies have evaluated oral mucosal lesions for CD44 expression and found a loss with invasive squamous cell carcinoma when compared to normal epithelium, hyperplasia, and squamous papillomas, which stained particularly strongly. To the best of our knowledge, no study has evaluated CD44 expression when comparing salivary ductal papillomas in comparison to oral papillary SCCA. In this study 18 cases of intraductal papilloma were compared to 19 cases of oral papillary SCCA. Within the ductal papilloma group, all cases stained either absent (6 %), weakly (33 %), or moderately (61 %) with 76 % expressing the stain diffusely and 24 % focally. In comparison, the papillary squamous cell carcinoma cases expressed the CD44 moderately (26 %) or strongly (74 %) with 100 % showing diffuse staining. Thus, the CD44 expression was contrary to expectation based on previous studies, which we hypothesize is due to the extremely well differentiated nature of papillary SCCA which expressed CD44 staining compatible with levels previously reported with oral squamous papillomas than invasive carcinoma.     

Primary signet ring cell carcinoma of bladder exemplifying vesical epithelial multipotentiality.

The eighth reported case of primary signet ring cell carcinoma of the urinary bladder is described clinically and pathologically. It is unusual because of complete replacement of the transitional epithelium by squamous and glandular metaplasia. The latter was particularly striking, demonstrating "normal" colonic mucosa, cystitis glandularis, well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and the rare signet ring cell carcinoma variant. The possible origin of such changes is discussed.     

Studies on antigen associated with human squamous cell carcinoma (SCC antigen) in patients with esophageal carcinoma

The authors studied on SCC antigen in patients with esophageal carcinoma. Serum SCC antigen was found in 9 (40.9%) of 22 patients with esophageal squamous cell carcinoma and 5 (55.5%) of 9 patients with lung squamous cell carcinoma, but was not found in other malignant diseases, such as gastric cancer, hepatoma, colon cancer, pancreas cancer and biliary try tract cancer. SCC antigen positive cases increased in association with progression of histological invasion, grade of nodal metastasis and clinical stage. However, in early esophageal carcinoma, SCC antigen was rarely positive. There was no positive case in patients with poorly differentiated squamous cell carcinoma regardless of clinical stage. Positive rate of SCC antigen increased in association with progression of clinical stage in patients with moderately and well differentiated squamous cell carcinoma. Immunoreactivity of SCC, which was investigated immunohistologically with TA-4 rabbit serum, was not found in cases with poorly differentiated squamous cell carcinoma, but was found in keratinized portion and cytoplasm of moderately and well differentiated carcinoma. From the above, SCC antigen is intimately related with keratinization of squamous cell carcinoma, and it was thought that it could be useful as a good marker for diagnosis of moderately and well differentiated squamous carcinoma of the esophagus.     

Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis.

BACKGROUND: The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma. METHODS: We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs. RESULTS: There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p =.04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p =.02) and in the group of SCCs (p =.01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p =.1) and was significantly associated with increased vascularization (p =.03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p =.02) and increased tumor vascularization correlated with higher cGMP levels (rs =.4; p =.01). CONCLUSIONS: Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC.     

Analysis of Immunohistochemical Expression of K19 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma Using Color Deconvolution-Image Analysis Method

K19 is an intermediate filament protein that has been investigated in oral squamous cell carcinoma (OSCC), but that has not been correlated with the amount of keratin produced within well-differentiated OSCC grade. The aim of the present study was to objectively analyze K19 immunoexpression in OSCC and to validate the utility of K19 in differentiation among grades of oral epithelial dysplasia (OED). Formalin-fixed tissues of 36 primary OSCC (22 well, 10 moderately, 4 poorly differentiated), 43 OED (23 mild, 8 moderate, 12 severe), and 11 normal oral epithelium (NOE) were included. K19 was immunostained using HRP-DAB method. The percentage of K19-positive area was found using color deconvolution program in ImageJ^® image analysis system (public domain software, National Institutes of Health, Bethesda, MD, USA) and analyzed using independent samples t tests and ANOVA test. K19 scores in NOE, mild, moderate and severe OED were: 1.8, 3.4, 21, and 50.3%, respectively, with significant association with the grade (t test P < 0.05). Well-differentiated OSCC with <30% keratin pearl formation expressed significantly higher K19 scores compared to well-differentiated OSCC with >30% keratin pearls (28.6 and 1.2%, respectively, P < 0.05). K19 scores in moderately and poorly differentiated OSCC were 60.8 and 61.3%, respectively. K19 scores significantly differentiated between two subgroups of tumors within well-differentiated OSCC grade and reflected histologic differentiation as well as probably predicting the clinical outcome. Combining K19 immunostain with the regular H&;E stain may be helpful to facilitate and assure assigning a more accurate grade for OED.     

A case of primary malignant neoplasms associated with penile cancer and prostatic cancer

A case of a 79-year-old man with penile cancer and prostate cancer is reported. The pathological study of surgical specimens disclosed well-differentiated squamous cell carcinoma of the penis and poorly differentiated adenocarcinoma of the prostate. This is a rare case of multiple primary malignant neoplasms associated with penile cancer and prostate cancer.     

结肠癌组织中CLDN7基因的表达及临床意义

目的探讨结肠癌组织中CLDN7基因的表达及临床意义。方法采用RT—PCR和免疫组化法检测40例结肠癌组织（实验组）及40例正常结肠黏膜组织（对照组）中CLDN7基因mRNA和蛋白的表达,比较两组间的差异,分析CLDN7的表达与结肠癌临床病理特征的关系。结果结肠癌组织中CLDN7 mRNA阳性表达率为30．0％（12／40）,明显低于正常结肠黏膜（P〈0．05）。结肠癌组织中CLDN7的免疫组化染色阳性表达率为22．5％（9／40）,也明显低于正常结肠黏膜（P〈0．05）;CLDN7表达与肿瘤组织的分化程度、浸润深度、淋巴结转移及临床分期等均有明显相关性（P〈0．05）。结论CLDN7在结肠癌组织中表达减低,且CLDN7的表达与结肠癌临床分期、淋巴结转移及分化程度关系密切。     

皮肤鳞状细胞癌中PCNA和PTEN的表达与临床病理特征的关系

目的:探讨PCNA和PTEN在皮肤鳞状细胞癌(SCC)中的表达情况,研究其表达与临床病理特征的关系。方法:采用免疫组化SP法检测52例皮肤鳞状细胞癌组织和10例正常皮肤组织石蜡标本中PCNA和PTEN蛋白的表达。结果:在SCC标本中,PCNA蛋白阳性表达率明显高于正常皮肤组织,PTEN蛋白阳性表达率明显低于正常皮肤组织(P<0.005)。PCNA蛋白的阳性表达与病理分级呈明显正相关(r=0.484),PTEN蛋白阳性表达与病理分级呈明显负相关(r=0.507),差异均有统计学意义(P<0.005);在低分化SCC标本中,PCNA蛋白的阳性表达率高于高中分化组,PTEN蛋白的阳性表达率低于高中分化组(P均<0.001);PCNA与PTEN蛋白的表达存在明显的负相关(r=0.557);两者表达均与年龄和部位无关(P>0.05)。结论:在SCC组织标本中,PCNA强表达,PTEN低表达或失表达,在SCC的发生、发展及转移过程中发挥重要作用,二者对于判断SCC的进展和预后具有重要的临床意义。     

Subdividing ovarian and peritoneal serous carcinoma into moderately differentiated and poorly differentiated does not have biologic validity based on molecular genetic and in vitro drug resistance data

Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinomas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84% of moderately and 70% of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.