子宫颈浸润性复层产黏液性癌1例并文献复习

目的探讨子宫颈浸润性复层产黏液性癌(invasive stratified mucin-producing carcinoma, ISMC)的临床病理学特征、诊断及鉴别诊断。方法观察1例ISMC的临床病理特征及免疫表型,并复习文献。结果患者女性,45岁,体检发现HPV16型阳性。大体上,于子宫颈处见一暗褐色菜花样新生物,大小2.0 cm×2.0 cm,似侵犯肌层。镜下肿瘤细胞类似于复层产黏液性上皮内病变(stratified mucin-producing intraepithelial lesion, SMILE),肿瘤排列呈巢团状,在间质内浸润性生长,可见促纤维增生性反应及炎细胞浸润。肿瘤周边可见原位腺癌(adenocarcinoma in situ, AIS)成分。肿瘤表面可见SMILE成分,局部可见SMILE累及腺体成分。PAS及AB染色阳性。免疫表型:肿瘤细胞CK7、p16及CEA弥漫强阳性,CK5/6及p63灶阳性,Ki-67增殖指数约80%。结论 ISMC是近年来提出的组织学形态类似于SMILE的浸润性肿瘤,尚未收入WHO(2014)女性生殖系统肿瘤的一种新的病理学实体肿瘤,易误诊为其他类型的癌,确诊需要结合组织病理学、免疫组化及特殊染色等综合分析。     

子宫颈浸润性复层产黏液的癌6例临床病理分析

目的 探讨子宫颈浸润性复层产黏液的癌(invasive stratified mucin-producing carcinoma, ISMC)的临床病理学特征及预后。方法 回顾性分析2019～2021年褔建省肿瘤医院诊治的6例子宫颈ISMC的临床病理学及免疫表型特征，并复习相关文献。结果 6例均可见经典的ISMC形态，实性癌巢由胞质内黏液多少不等的复层上皮细胞组成，边界较圆钝，巢周细胞呈栅栏状排列，类似子宫颈产黏液的复层上皮内病变。转移灶与原发灶形态一致或癌巢较不规则。免疫表型：肿瘤细胞p16、CEA、CK7、CK8/18均阳性，ER、PR、PAX8和Syn均阴性，CK5/6、p40阴性或灶性阳性，Ki-67增殖指数为70%～80%。结论 子宫颈ISMC是新近命名的HPV相关的腺癌亚型，具有独特的形态学及免疫表型特征，预后较其它HPV相关腺癌差，识别子宫颈癌中ISMC成分具有临床意义。     

宫颈浸润性复层产黏液癌临床病理学分析

目的探讨宫颈浸润性复层产黏液癌(invasive stratified mucin-producing carcinoma,ISMC)的临床病理学特点及鉴别诊断。方法回顾性分析陆军军医大学大坪医院病理科2019年1月至2021年5月间诊断的10例宫颈ISMC临床病理学特征,并复习相关文献。结果10例患者年龄范围26~59岁,平均年龄46岁。大部分患者有阴道流血、阴道流液或下腹坠胀等临床症状,少部分患者经体检发现。6例手术切除患者的临床分期:ⅠB1期3例,ⅠB2期1例,ⅢC1期1例,ⅢC2期1例。形态上,10例均可见假复层的柱状细胞形成侵袭性的巢团结构,周围肿瘤细胞呈栅栏状排列,可见数量可变含胞质内黏液的肿瘤细胞,凋亡小体和有丝分裂象易见;也可见其他的结构特征,如假腺腔、乳头及实性片状不伴周围的栅栏状排列。细胞形态上可见如嗜酸性细胞质、透明细胞质、组织细胞样及鳞状分化细胞。4例伴原位腺癌和/或高级别鳞状上皮内病变和/或复层产黏液性上皮内病变。手术切除的6例,均为Silva C型浸润模式,3例纯ISMC(3/6),2例混合了人乳头状瘤病毒(HPV)相关性普通型腺癌,1例混合小细胞神经内分泌癌,淋巴结转移2例(2/6)。所有病例均弥漫强阳性表达p16,Ki-67阳性指数50%~90%。不同比例的肿瘤细胞过碘酸雪夫染色及阿辛蓝染色阳性。结论ISMC属于HPV相关宫颈腺癌,相对少见。ISMC具有广泛的形态学谱系,近半数病例为混合性ISMC,易误诊为宫颈的其他恶性肿瘤。与其他腺癌相比,ISMC更常表现出破坏性间质浸润及淋巴结转移。     

宫颈浸润性复层产黏液癌临床病理学分析

目的探讨宫颈浸润性复层产黏液癌(invasive stratified mucin-producing carcinoma,ISMC)的临床病理学特点及鉴别诊断。方法回顾性分析陆军军医大学大坪医院病理科2019年1月至2021年5月间诊断的10例宫颈ISMC临床病理学特征,并复习相关文献。结果10例患者年龄范围26~59岁,平均年龄46岁。大部分患者有阴道流血、阴道流液或下腹坠胀等临床症状,少部分患者经体检发现。6例手术切除患者的临床分期:ⅠB1期3例,ⅠB2期1例,ⅢC1期1例,ⅢC2期1例。形态上,10例均可见假复层的柱状细胞形成侵袭性的巢团结构,周围肿瘤细胞呈栅栏状排列,可见数量可变含胞质内黏液的肿瘤细胞,凋亡小体和有丝分裂象易见;也可见其他的结构特征,如假腺腔、乳头及实性片状不伴周围的栅栏状排列。细胞形态上可见如嗜酸性细胞质、透明细胞质、组织细胞样及鳞状分化细胞。4例伴原位腺癌和/或高级别鳞状上皮内病变和/或复层产黏液性上皮内病变。手术切除的6例,均为Silva C型浸润模式,3例纯ISMC(3/6),2例混合了人乳头状瘤病毒(HPV)相关性普通型腺癌,1例混合小细胞神经内分泌癌,淋巴结转移2例(2/6)。所有病例均弥漫强阳性表达p16,Ki-67阳性指数50%~90%。不同比例的肿瘤细胞过碘酸雪夫染色及阿辛蓝染色阳性。结论ISMC属于HPV相关宫颈腺癌,相对少见。ISMC具有广泛的形态学谱系,近半数病例为混合性ISMC,易误诊为宫颈的其他恶性肿瘤。与其他腺癌相比,ISMC更常表现出破坏性间质浸润及淋巴结转移。     

卵巢浆黏液性癌4例临床病理分析

目的探讨卵巢浆黏液性癌的临床病理学特征、免疫表型、诊断及鉴别诊断。方法回顾性分析4例卵巢浆黏液性癌的临床资料、病理学特征、免疫表型等,并复习相关文献。结果 4例患者年龄44～57岁,平均49岁。临床表现主要为腹痛或腹胀。肿瘤最大径8～17 cm,平均13 cm。2例为双侧,2例为单侧,均呈囊实性,囊内壁可见乳头状赘生物并含黏稠液体。镜下见肿瘤由浆液性上皮、子宫颈管黏液性上皮及透明细胞混合组成以复杂的乳头为主伴腺样、筛状或实性结构,间质及腺腔内见多量中性粒细胞浸润。免疫表型:肿瘤细胞ER(4/4)、PR(3/4)、CK7(4/4)、PAX8(4/4)、p16(3/4)、vimentin(4/4)、CEA(2/4)均阳性,p53呈突变型阳性,CK20、CDX2、HNF1β、WT-1均阴性。PAS染色及DPAS染色均阳性。TNM/FIGO分期:ⅠA期2例,ⅠB期1例,ⅠC期1例。随访9～42个月,1例术后22个月死亡,3例无复发。结论卵巢浆黏液性癌有其独特临床病理特征,需与卵巢其他上皮性肿瘤鉴别。     

直接免疫组织化学染色在术中冷冻切片细支气管腺瘤辅助诊断中的应用价值

目的探讨直接免疫组织化学染色技术提高术中肺肿瘤疑难病例细支气管腺瘤(bronchiolar adenoma, BA)诊断准确性的可行性及应用价值。方法选取2021年1月至7月中国医学科学院肿瘤医院CT提示单发或多发肺磨玻璃结节或实性结节, 术中单纯依靠冷冻HE切片肺肿瘤鉴别诊断困难病例共19例, 实验组采用直接免疫组织化学染色细胞角蛋白5/6(CK5/6)和p63在冷冻切片中基底细胞的表达情况, 辅助术中肺肿瘤疑难病例BA与原位/微小浸润腺癌/腺癌/浸润性黏液腺癌鉴别;对照组为两名诊断医师对这19例病例进行常规冷冻HE切片诊断。两组均以石蜡切片诊断结果为金标准, 评价实验组与对照组BA诊断的灵敏度、特异度、与石蜡切片诊断的一致性及冷冻切片诊断耗时。结果 CK5/6、p63染色显示BA存在基底细胞;在原位/微小浸润腺癌/腺癌/浸润性黏液腺癌中不存在基底细胞。实验组中直接免疫组织化学染色对术中疑难病例BA的灵敏度为100%、特异度为86.7%, 冷冻与石蜡切片诊断的一致性Kappa值为0.732, 均显著高于对照组(P<0.05)。实验组术中冷冻切片诊断平均耗时(32.4 min)比...     

宫颈腺癌和腺上皮内肿瘤组织中PTEN基因的突变和蛋白表达

目的 探讨PTEN基因的突变和表达在宫颈腺癌发生中的作用.方法 应用免疫组织化学SP法检测42例宫颈腺癌、20例宫颈腺上皮内肿瘤和28例正常宫颈组织中PTEN蛋白表达,并采用聚合酶链反应-单链构象多态性(PCR-SSCP)法检测上述组织中PTEN基因第5、8外显子突变情况.结果 宫颈腺癌、宫颈腺上皮内肿瘤和正常宫颈腺上皮组织中PTEN蛋白的阳性表达率分别为54.8%(23/42)、25.0%(5/20)和100%(28/28),其差异均有统计学意义(P<0.05);黏液型和子宫内膜型宫颈腺癌组织中PTEN蛋白阳性表达率分别为9/19和2/10,其他组织学变型PTEN蛋白阳性表达率92.3%(12/13).宫颈腺癌、宫颈腺上皮内肿瘤和正常宫颈组织中PTEN基因第5、8外显子的突变率分别为19.0%(8/42)、45.0%(9/20)和0,其差异均有统计学意义(x<,2>=4.29,x2=12.70;均P<0.05);黏液型和子宫内膜型宫颈腺癌PTEN基因第5、8外显子的突变率分别为4/19和4/10,其他组织学变型未检测到突变.结论 宫颈腺癌的发生与PTEN基因的突变和蛋白表达产物缺失有关,PTEN基因的突变和蛋白表达产物缺失可能是宫颈腺癌发生中的早期事件.     

子宫颈产黏液的复层上皮内病变4例临床病理分析

目的探讨子宫颈产黏液的复层上皮内病变(stratified mucin-producing intraepithelial lesion,SMILE)的临床病理特征、诊断及鉴别诊断。方法对4例SMILE进行回顾性分析,观察其组织学特征、免疫表型及超微结构特点,并进行相关文献复习。结果 4例SMILE均为女性,年龄32～49岁。病变组织在镜下均见异型增生的复层上皮细胞,核深染;可见明显的黏液细胞,胞质空泡状;核分裂象及凋亡小体常见。其中3例伴子宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)或子宫颈原位腺癌(adenocarcinoma in situ,AIS),1例为单纯性SMILE。免疫表型:4例肿瘤细胞p16胞核与胞质阳性,CAM5. 2胞质弥漫阳性,2例IMP3阴性、2例IMP3阳性,4例p63、p40均为部分肿瘤巢基底部上皮细胞表达,Ki-67增殖指数20%～60%。2例获得细胞学随访,均未见复发;2例失访。结论 SMILE不同于HSIL或AIS,有其独立的病理组织学特征,需与子宫颈鳞状上皮内病变、腺上皮病变及未成熟鳞状化生等鉴别。     

肺原发性良性黏液上皮性病变冷冻切片误诊为黏液腺癌12例分析

目的探讨冷冻切片误诊为黏液腺癌的良性黏液上皮性病变的病理形态学特征,并分析联合使用免疫组化标记CK5/6及p63的鉴别诊断价值。方法收集宁波临床病理诊断中心2011年8月～2018年1月冷冻切片误诊为黏液腺癌的良性黏液上皮性病变12例,行CK5/6、p63免疫组化染色。结果冷冻切片误诊的12例病变最大径为0.4～1.2 cm,平均0.8 cm,病变边界清楚,黏液上皮间可见纤毛柱状上皮(12/12),CK5/6及p63标记可见完整的基底细胞层(12/12)。12例中,位于肺外周9例,位于肺中央区3例。结论良性黏液上皮性病变都具有双层结构,黏液上皮之间可见到纤毛柱状上皮,细胞缺乏异型性,当病变位于肺外周,黏液上皮丰富,纤毛柱状上皮零散分布时易误诊为黏液腺癌。     

胰腺黏液性非囊性腺癌

目的探讨胰腺黏液性非囊性腺癌的病理形态学特征和相关蛋白表达状态与生物学行为的关系。方法对249例胰腺外分泌癌中6例符合黏液性非囊性腺癌病例进行形态学观察,应用免疫组织化学EnVision法检测了p21^ras、p21^WAF1、p16、p33^ING1、p53、ATM、MDM2、增殖细胞核抗原(PCNA)和细胞周期蛋白(Cy)D1、D3、A、B和E的表达,AB-PAS染色观察细胞内外黏液分布,同时对6例进行生存期随访。结果6例全部位于胰头部位,4例有十二指肠浸润,2例肝转移,2例局部淋巴结转移,1例周围神经浸润,具有相似的组织学特征。免疫组织化学染色阳性为p21^ras 5例,p21^WAF1 3例,p16 1例,p33^ING1 4例,p53 2例,ATM 3例,MDM2 3例,PCNA 6例,CyA 3例,CyD1 3例,CyD3 4例,CyB 4例,CyE 6例。AB-PAS染色见细胞内、外黏液分布。随访结果2例死亡(分别为术后14、20个月),3例存活(分别为28、49、87个月),1例失访。结论胰腺黏液性非囊性腺癌具有一些独特的病理形态学特征和生物学行为,肿瘤细胞存在多种肿瘤相关蛋白的改变和细胞周期蛋白的过表达,显示较差的生物学行为和较强的侵袭能力,但预后可能比普通导管腺癌好。     

Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE

Stratified mucin-producing intraepithelial lesion (SMILE) is a histologic subtype of HPV-associated endocervical adenocarcinoma in situ. We have observed benign endocervical changes resembling SMILE. We aim to characterize this pattern and explore its potential association with dysplasia. We retrospectively retrieved all 296 consecutive cases accessioned as endocervical biopsies. Some included multiple specimens, totaling 483 biopsies and 219 endocervical curettages (ECC), n = 702. We included cases showing endocervical epithelial stratification often with pencillate (triangular-shaped) nuclei. We rejected cases in which layering represented tangential sectioning, metaplasia, microglandular hyperplasia, gastric type epithelial changes, and dysplasia. We found benign stratified intraepithelial mucinous proliferation in 51 patients, either with a multilayered (n = 27) or a two-layered appearance (n = 24). Overall, multilayered proliferation occurred in 6 % (29/483) of biopsies and in 0.9 % of ECCs (2/219). Two-layering was identified in 4 % of all biopsies (20/482) and was not seen in ECCs. Histologic findings included stratification, intracytoplasmic mucin, paler cytoplasm, low nuclear-to-cytoplasmic ratio, often pencillate nuclei, rare mitoses, and no apoptotic bodies. P16 immunohistochemistry (n = 12) was negative, suggesting absence of underlying high-risk HPV infection. HSIL was concomitant in 29.6 % (8/27) of patients with multilayered proliferation. Concurrent SMILE was not observed. We also reviewed 13 SMILE cases. Concurrent multilayered benign proliferation was identified in 54 % (7/13) of cases. We describe benign stratified intraepithelial mucinous proliferation of the cervix, which morphologically may overlap with SMILE. Its presence in most SMILE cases suggests a potential relationship. The multilayered form represents a diagnostic pitfall when mitotically active. Because of the often-coexistent HSIL, we propose that its presence should prompt scrutiny to rule out any associated dysplasia.     

Kategorisierung der Tumoren der Cervix uteri

In the 2014 WHO classification, squamous cell precursor lesions are classified as low-grade and high-grade intraepithelial lesions. LSIL corresponds to CIN1, HSIL includes CIN2 and CIN3. Only adenocarcinoma in situ (AIS) is accepted as precursor of adenocarcinoma and includes the stratified mucin-producing intraepithelial lesion (SMILE). Although relatively rare, adenocarcinoma and squamous cell carcinoma can be mixed with a poorly differentiated neuroendocrine carcinoma. Most cervical adenocarcinomas are low grade and of endocervical type. Mucinous carcinomas show marked intra- and extracellular mucin production. Almost all squamous cell carcinomas, the vast majority of adenocarcinomas, and many rare carcinoma types are HPV related. For low grade endocervical adenocarcinomas, the pattern-based classification according to Silva should be reported. Neuroendocrine tumors are rare and are classified into low-grade and high-grade, whereby the term carcinoid is still used.     

Expression of c-erbB-2 oncoprotein in mammary and extramammary Paget's disease.

Formalin-fixed, paraffin-embedded tissue sections from 45 patients with mammary and extramammary Paget's disease were stained immunohistochemically with the use of a polyclonal antiserum directed against a 14-amino acid segment of the c-erbB-2 oncoprotein. Positive membrane staining, which correlates with gene amplification, was found in 15 of 19 cases (79%) of mammary Paget's disease, 4 of 13 cases (31%) of vulvar Paget's disease, none of 8 cases of scrotal Paget's disease, and none of 5 cases of perianal Paget's disease. Of the 19 patients with mammary Paget's disease, specimens of underlying breast tissue were available from 14; all contained a concurrent ductal adenocarcinoma. Concordance of c-erbB-2 antigen staining between the underlying breast carcinoma and the pagetoid component was observed in 12 cases. Of the 13 patients with vulvar Paget's disease, 2 had superficial stromal invasion, and 3 had underlying, deeply invasive adenocarcinomas. One superficially invasive case was positive for c-erbB-2 expression. One additional case of vulvar Paget's disease had an associated primary pagetoid endocervical adenocarcinoma that spread into the endometrium; both the endocervical and vulvar components stained positively for the c-erbB-2 antigen. The results of this study indicate that the c-erbB-2 oncoprotein may play a role in the pathogenesis of extramammary Paget's disease. These results also suggest that the c-erbB-2 oncoprotein may function in vivo to promote intraepithelial spread of adenocarcinoma cells.     

Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.     

High-risk human papillomavirus DNA testing: a marker for atypical glandular cells

Cervical/endocervical cytology screening has decreased morbidity and mortality, and implementing adjunctive human papilloma virus (HPV) DNA testing for atypical squamous cells of undetermined significance has improved the specificity for detecting premalignant squamous lesions. Currently, there are no guidelines to perform HPV DNA testing on cervical/endocervical ThinPreps with atypical glandular cells (AGC). To assess the potential role of HPV DNA testing on AGC cases, Hybrid Capture 2 (Digene Corp.) testing was performed on 144 cervical/endocervical AGC specimens. One hundred three of 144 cases had follow-up; 60/103 (58.3%) were high-risk HPV negative and 43/103 (42.3%) were high-risk HPV positive. Of 43 HPV-positive patients, 37 had adenocarcinoma in situ (AIS), atypical squamous cells of undetermined significance (ASCUS), or cervical squamous intraepithelial neoplasia, while only one patient without high-risk HPV had a squamous intraepithelial neoplasia. Furthermore, most high-risk HPV positive AGC cases harbored high-grade squamous intraepithelial lesion (HSIL) rather than AIS. Our data support HPV DNA testing of all AGC specimens to detect cervical, especially squamous, neoplasia.     

Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarray.

A multistep model for pancreatic adenocarcinoma has been proposed recently. In this model, well-defined, noninvasive ductal lesions are recognized as precursors of invasive cancer and have been classified under the nomenclature of pancreatic intraepithelial neoplasia, or PanIN. Increasing evidence suggests that PanINs represent true neoplasms of the pancreatic ductal epithelium, accumulating histologic and genetic abnormalities in their progression toward invasive cancer. We have constructed a tissue microarray containing 55 PanIN lesions of all histologic grades in order to perform a multicomponent analysis of the pancreatic adenocarcinoma progression model. The protein products of 14 genes encompassing a variety of functional classes, such as tumor suppressor genes (p53, Smad4/Dpc4), oncogenes (beta-catenin), cell cycle antigens (p16, cyclin D1), proliferation antigens (Ki-67, topoisomerase II alpha), and epithelial apomucins (MUC1, MUC2, MUC5), as well as "novel" genes described as differentially up-regulated in invasive pancreas cancer by global microarray expression analysis (mesothelin, prostate stem cell antigen, fascin, and 14-3-3varsigma), were analyzed by immunohistochemistry on the PanIN tissue microarray. Comparison of the results from the current study with previously published data performed on routine histologic sections of PanINs demonstrates that tissue microarrays are a valid platform for molecular analysis not only of invasive cancers but of precursor lesions as well. In addition, this study demonstrates that molecular abnormalities in PanINs are not random but can usually be stratified into "early" changes (e.g., expression of MUC5 and prostate stem antigen, or loss of p16), "intermediate" changes (e.g., expression of cyclin D1), and "late" changes (e.g., expression of p53, proliferation antigens, MUC1, mesothelin, and 14-3-3varsigma, or loss of Smad4/Dpc4). Understanding the molecular pathogenesis of precursor lesions of invasive pancreatic adenocarcinomas using a high-throughput tissue microarray-based approach is a valuable adjunct to designing rational strategies for early detection of this lethal neoplasm.     

Evaluation of p16INK4a and pRb expression in cervical squamous and glandular neoplasia

p16(INK4a) is known to play a critical role as a negative regulator of cell cycle progression and differentiation by controlling the activity of the tumor-suppressor protein pRb. The present study evaluated the expression of p16(INK4a) and pRb in cervical squamous and glandular neoplasia. Immunohistochemical staining was performed for p16(INK4a) and pRb in formalin-fixed, paraffin-embedded tissue sections of the uterine cervix using an indirect immunoperoxidase method. p16(INK4a) staining was detected in 7 of 108 sections (6.5%) of normal squamous mucosa, in scattered ciliated columnar cells in 33 of 88 sections (37.5%) of normal endocervical glands, in 9 of 30 sections (30%) with Nabothian cysts, and in 4 of 4 areas (100%) of tubal metaplasia. In contrast, strong p16(INK4a) staining was found in 13 of 18 cases (72.2%) of cervical intraepithelial neoplasia (CIN) I and in all cases of CIN II/III (n = 46), squamous cell carcinoma (n = 18), endocervical glandular dysplasia (n = 10), adenocarcinoma in situ (n = 23), and invasive adenocarcinoma (n = 12). pRb expression was detected in each diagnostic category; however, the proportion of pRb-positive cells was relatively decreased in high-grade premalignant and malignant lesions of the squamous and endocervical mucosa and showed a generally inverse correlation with the expression of p16(INK4a) at the tissue level. These findings confirm a correlation between the expression of p16(INK4a) and pRb in cervical neoplasias and indicate that p16(INK4a) is a specific marker for premalignant and malignant lesions of the squamous and endocervical mucosa.     

Endocervical glandular dysplasia, adenocarcinoma in situ, and early invasive (microinvasive) adenocarcinoma of the uterine cervix

The pathological features of endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS), and early invasive (microinvasive) adenocarcinoma are reviewed. The histology and histochemistry of normal endocervical epithelium is discussed. The association of human papillomavirus (HPV) with the precursor lesions of invasive adenocarcinoma is examined. In the section on AIS, particular areas discussed include topography, immunohistochemistry, ploidy, and differential diagnosis. A management plan for AIS, EGD, and AIS with early invasion is presented.     

MUC4 is increased in high grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio

BACKGROUND: Patients with Barrett's oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. AIMS: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. METHODS: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. RESULTS: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. CONCLUSIONS: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.