p16蛋白与HPV mRNA检测在口咽部鳞状细胞癌诊断中的意义

目的 探讨p16蛋白与HPV mRNA检测在口咽部鳞状细胞癌(oropharyngeal squamous cell carcinoma, OPSCC)诊断中的意义。方法 收集2019年11月～2021年10月首都医科大学附属北京同仁医院诊治的105例OPSCC,采用免疫组化EnVision两步法检测p16、Ki-67、p53蛋白表达，并检测其中61例HPV16/18 mRNA的表达，分析其与临床病理特征的关系。结果 105例OPSCC中p16蛋白阳性58例(55.24%),阴性47例(44.76%);p16蛋白阳性患者比阴性患者的吸烟、饮酒史比例低(26/58 vs 37/47,16/58 vs 31/47),以扁桃体为常见发病部位(51/58 vs 18/47),易出现淋巴结转移(43/58 vs 23/47),Ki-67增殖指数较高(73.10%vs 47.45%),p53多为野生型(57/58 vs 16/47),形态学特征以非角化型鳞状细胞癌为主(29/58 vs 15/47),差异均有统计学意义(P<0.05)。61例HPV mRNA检测结果与p16蛋白表达完全一致(...     

《临床与实验病理学杂志》2003年第19卷关键词索引

AAs2 O3 　As2 O3 诱导胃癌细胞凋亡及细胞骨架改变病理学观察 (4 ) :4 16癌 ,Merkel细胞　转移性Merkel细胞癌 (6 ) :6 5 5癌 ,透明细胞　子宫内膜透明细胞癌组织学和免疫组织化学研究 (2 ) :14 9癌 ,嫌色细胞　肾嫌色细胞癌 4例临床病理分析及文献复习 (2 ) :2 17BBowen样丘疹病　外阴Bowen样丘疹病 15例临床病理分析 (1) :5 6鼻咽肿瘤　引物介导原位标记技术在检测鼻咽癌石蜡切片HPV DNA的应用 (2 ) :2 13鼻肿瘤　鼻腔和鼻旁窦非嗜铬性副神经节瘤 1例 (4 ) :4 5 0表面活性剂　表面活性剂在免疫组化中的应用 (6 ) :6 6 5C成纤维细…     

乳腺黏液囊肿样病变临床病理特征分析

目的探讨乳腺黏液囊肿样病变的临床病理特征及其诊断和鉴别诊断。方法对9例乳腺黏液囊肿样病变进行临床病理分析。以SP法对细胞角蛋白AE1／AE3、平滑肌肌动蛋白（SMA）、p63、c-erbB-2和053进行免疫组织化学染色,组织化学为AB和PAS法染色。结果患者均为女性,年龄23-43岁（平均34岁）,乳腺均可触及肿物。肿物切面呈多囊性胶冻样。镜下可见多发性、充满黏液的囊肿,囊腔衬覆扁平-立方-柱状上皮,其中3例上皮有乳头状增生,1例有不典型增生。间质内可见黏液湖,其内无漂浮细胞。囊内及间质黏液呈AB及PAS染色阳性。囊肿衬覆上皮细胞及2例黏液湖内漂浮的上皮细胞团AE1／AE3阳性。囊肿上皮细胞外侧扁平肌上皮呈SMA、p63阳性。c-erbB-2和p53染色均阴性。结论乳腺黏液囊肿样病变是一种独立的良性病变,容易误诊,需与黏液癌等肿瘤进行鉴别。     

子宫颈HPV相关性乳头状鳞状细胞癌的临床病理分析

目的 探讨子宫颈乳头状鳞状细胞癌(papillary squamous cell carcinoma, PSCC)的临床病理学特征、诊断及鉴别诊断。方法 收集18例子宫颈PSCC临床资料,行HE和免疫组化染色,分析其临床病理特征,并复习相关文献。结果 18例患者年龄30～71岁,平均49岁,镜下活检和手术标本均可见浅表乳头状结构,伴纤维血管轴心,被覆上皮具有子宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion, HSIL)的特征。17例子宫颈活检病理学检查均为典型的PSCC,1例子宫颈虽有菜花样肿物,但活检标本未见间质浸润,行子宫颈锥切,锥切标本仍未见间质浸润。13例行根治性子宫切除,最后均诊断为子宫颈PSCC,伴间质浸润;4例活检诊断后失访。免疫表型：p16呈弥漫强阳性(块状)染色,p63、CK7阳性,CK20阴性,Ki-67增殖指数>90%,遍布上皮全层。14例行HPV DNA分型检测,其中10例HPV 16阳性(71.4%),2例分别合并HPV 53和HPV 59感染。结论 子宫颈PSCC具有典型的病理形态学表现,...     

血管免疫母细胞性淋巴结病/淋巴瘤的回顾性分析

目的 探讨血管免疫母细胞性淋巴结病(AILD)和血管免疫母细胞性淋巴瘤(AITL)的临床及病理学特征，以及p53蛋白在AILD和AITL中表达的临床意义。方法 对原诊断AILD 9例阳AITL 9例重新复查病理切片及临床资料．采用免疫组织化学SP法，对复验后的病例进行免疫表型标记及p53蛋白检测。结果 AILD的误诊率5/9、AITL的误诊率5／9。AILD 4例中p53阳性表达1例，AITL 7例中p53阳性表达5例。结论 误诊的最主要原因是对AILD和AITL的诊断标准掌握不够准确，它们与一些有类似形态结构肿瘤的主要区别在于有高度增生的分支状小血管，呈弥漫性分布．在AILD和AITL的鉴别诊断中，p53可作为一个重要的免疫学指标。     

基因重排分析与p53的表达在判定血管免疫母细胞性淋巴结病性质上的意义

目的探讨基因重排和p53表达在判定血管免疫母细胞性淋巴结病(AIL)的病变性质上的意义。方法运用聚合酶链反应(PCR)技术检测44份AIL石蜡包埋组织标本中IgH及TCRγ基因重排情况,采用免疫组织化学ABC法染色技术检测AIL免疫表型及p53蛋白表达。并对35例进行了随访。结果44份AIL标本中,12份（27.3%）检测出TCRγ基因重排,2份（4.5%）IgH基因重排,2份（4.5%）IgH与TCRγ基因双重排。14份AILp53蛋白表达阳性,其中12份为IgH或TCRγ基因重排阳性。基因重排阳性组与阴性组对比,p53蛋白表达差异有非常显著性意义(P<0.01)。11例基因重排阳性患者中8例1年内死亡,随访至18个月时3例存活;24例基因重排阴性患者中,仅3例1年内死亡,余21例随访时仍存活,最长达96个月。结论AIL是一种临床病理综合征;基因重排能准确地判定其病变性质;p53蛋白表达与AIL基因重排有关,是判定AIL病变性质的重要免疫学指标。     

子宫颈腺样基底细胞癌4例临床病理观察

目的探讨子宫颈腺样基底细胞癌的临床病理特征、诊断、鉴别诊断及预后特点,以提高对该病的认识及避免过度治疗。方法对4例子宫颈腺样基底细胞癌的临床及病理资料进行回顾性分析,运用常规HE、免疫组化EnVision法染色及原位杂交技术进行检测,并复习相关文献。结果 4例子宫颈腺样基底细胞癌患者年龄53~67岁,平均61.5岁,4例患者均行全子宫+双侧附件切除术。镜下见癌组织由形态单一、分化良好的基底样小细胞组成,排列成小巢状或条索状。癌巢周边见栅栏状排列的细胞核,部分癌巢中央形成囊性腔隙,也可见腺样或鳞状分化。4例患者均伴子宫颈上皮内病变(cervical intraepithelial neoplasia,CIN)。免疫表型:肿瘤细胞CK5/6、CK8/18、CK19、p16、p40、p53、BCL-2和p63均阳性,ER、CK7、CEA、CD117和S-100均阴性。原位杂交检测:HPV16/18阳性。4例患者随访19~62个月,均未见复发及转移。结论子宫颈腺样基底细胞癌属于罕见但预后较好的肿瘤,因预后不同,需与腺样囊性癌、基底样鳞状细胞癌、神经内分泌癌及腺鳞癌鉴别。治疗可选择全子宫切除术或宫颈锥切术,不推荐放、化疗。     

子宫内膜原发性胃(胃肠)型黏液腺体病变临床病理学分析

目的探讨子宫内膜原发性胃(胃肠)型黏液腺体病变的临床和病理学特征。方法回顾性分析复旦大学附属妇产科医院2014—2022年诊治的8例子宫内膜原发性胃(胃肠)型黏液腺体病变病例的临床病史和病理资料, 复习所有病理切片, 并随访。结果 8例患者年龄35～67岁, 平均年龄55.5岁。7例患者术前查高危型人乳头状瘤病毒(HPV), 其中1例患者高危型HPV 52型阳性。所有患者均未发现宫颈黏液性病变。2例为浸润性胃(胃肠)型黏液腺癌, 2例为良性胃(胃肠)型黏液化生, 余4例为不典型胃(胃肠)型黏液腺体增生。镜下肿瘤细胞具有胃(胃肠)型分化的黏液上皮特征。免疫表型显示5例MUC6弥漫或局灶阳性, 3例细胞角蛋白20和CDX2阳性。5例p16阴性或斑驳阳性, 1例弥漫强阳性表达。雌激素受体在良性病变及不典型病变中表达, 在浸润性腺癌中局灶弱阳性或阴性。p53在1例中呈突变型表达, 余均呈野生型表达。HPV原位杂交阴性。结论子宫内膜原发性胃(胃肠)型黏液腺体病变可以出现胃肠型分化的各种形态, 与高危型HPV感染无关, 形态学结合免疫组织化学有助于诊断。子宫内膜原发性胃(胃肠)型黏液腺体病变需排除...     

粘液表皮样癌p16、p53、nm23蛋白及其mRNA表达的临床病理意义

目的：了解粘液表皮样癌中p16、p53、nm23蛋白及其mRNA表达的情况,探讨它们与粘液表皮样癌的病理形态学特征的关系。方法：用HE和组织化学方法对41例粘液表皮样癌诊断,并按WHO标准分为高分化、低分化两组,用免疫组织化学SABC法和原位杂交方法,分别检测41例粘液表皮样癌p16、p53、nm23蛋白及mRNA,用统计学方法分析它们之间的关系。结果：粘液表皮样癌中低分化组,高分化组的p16蛋白失表达率分别是62．5％（15／24）和29．4（5／17）,P＝0．037;p53蛋白的阳性率分别为70．8％（17／24）和23．5％（4／17）,P＝0．003;nm23蛋白的阳性率分别为37．5％（9／24）和64．7（11／17）P＝0．086。p16、p53、nm23mRNA的表达与病理分级无明显相关。结论：p16、p53、nm23mRNA表达与病理分级无明显相关。     

子宫和卵巢腺瘤样瘤的临床病理分析

目的 探讨女性生殖系统腺瘤样瘤的发生、免疫组织化学表达的特征及鉴别诊断。方法 对24例子宫和卵巢腺瘤样瘤进行临床病理及免疫组织化学观察。结果 24例患者中腺瘤样瘤发生于子宫者21例,卵巢者2例,子宫与卵巢同时发生者1例,分别占本院同期子宫及卵巢肿瘤及瘤样病变的0.34%和0.06%。免疫组织化学染色显示：波形蛋白及细胞蛋白（AE1／AE3）均为阳性,呈双相表达;第八因子相关抗原（FⅧRAg)均为阴性;S－100蛋白20例阳性（83.3%),上皮膜抗原（EMA）4例阳性（16.7%);其中10例行calretinin蛋白染色,均为阳性表达。结论 女性生殖系统腺瘤样瘤为间皮起源,子宫为最常见部位。免疫组织化学染色结果可作为诊断及鉴别诊断的重要参考依据。其生物学行为为良性,预后良好。     

Relation between retinoblastoma and p53 proteins in human papilloma viruses 16/18 positive and negative cancers of the uterine cervix.

AIM: To ascertain the extent of retinoblastoma protein (pRB) expression in comparison to p53 protein and human papilloma viruses (HPV) 16/18 status in cervical carcinomas. METHODS: Fifty cases of invasive cervical carcinoma were HPV typed for genotypes 16 and 18 using consensus primers by polymerase chain reaction (PCR). Immunohistochemistry for pRB and p53 was done on formalin fixed tissue using microwave antigen retrieval and commercially available antibodies. RESULTS: Forty five cases were squamous carcinomas, three were adenocarcinomas, and two were adenosquamous carcinomas. Thirty one cases were HPV 16 positive and one was HPV 18. Sixteen cases showed +4 pRB expression and a further 11 were +3 positive. Seven cases were negative. Only five cases (10%) showed +4 p53 immunostaining, while seven were negative and 15 were +1. Of the 16 pRB +4 positive cases, one was negative for p53 and a further seven were +1 positive. This inverse pattern of staining between pRB and p53 had a p value of < 0.001. No correlation was observed between HPV 16/18 status and p53 and/or pRB staining. CONCLUSIONS: pRB is expressed in the majority of cases of cervical cancer (86%), with more than 75% (+4) of the tumour cell population being positive in 16 cases (32%). There appears to be a general inverse pattern of staining between pRB (high) and p53 (low) in cervical cancer. The expression of both pRB and p53 proteins is independent of the HPV 16/18 status of the tumour.     

p53 immunoreactivity in cervical intraepithelial neoplasia and non-neoplastic cervical squamous epithelium.

AIMS--To determine the pattern of p53 immunoreactivity in cervical squamous epithelium and to investigate the relation between p53 immunostaining and human papillomavirus (HPV) infection. METHODS--Immunocytochemistry for p53 was performed in 65 specimens of formalin fixed, paraffin wax embedded cervical tissue using a polyclonal antibody against recombinant p53. Microwave oven heating was used for antigen retrieval. Eight normal biopsy specimens, eight cases with histological features of HPV infection, and 49 cases of cervical intraepithelial neoplasia (CIN) were examined. Thirty one cases of CIN were examined. Thirty one cases of CIN were examined for evidence of HPV infection using in situ hybridisation with probes directed against wide spectrum HPV, HPV 16 and HPV 18. RESULTS--p53 immunoreactivity was seen in seven of eight (87%) of specimens with histological features of HPV infection, five of eight (62%) normal specimens, 13 of 22 (59%) CIN III, three of 14 (21%) CIN II and five of 13 (38%) CIN I specimens. The numbers of positive nuclei were small in cases of CIN and the location of positive nuclei within the epithelium paralleled the degree of dysplasia. Eleven of 15 (73%) CIN specimens which were immunoreactive for p53 yielded a positive signal for HPV by in situ hybridisation. A positive signal for HPV was also seen in 10 of 16 (63%) of CIN specimens in which p53 staining was absent. CONCLUSIONS--p53 immunoreactivity can be demonstrated in a small proportion of cells in the cervical squamous epithelium in a significant proportion of cases of CIN. This immunoreactivity seems to be independent of the presence of HPV, as assessed by in situ hybridisation. p53 immunoreactivity also occurs in non-neoplastic cervical squamous epithelium with a pattern of distribution within the epithelium which differs from that seen in CIN. Antigen retrieval by microwave oven heating enhances p53 immunostaining and may result in visualisation of cellular p53 in the absence of mutation.     

Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53 . We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion ( P = 0.032) or metastatic disease ( P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells ( P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells ( P = 0.05).
Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.     

Search for accumulation of p53 protein and detection of human papillomavirus genomes in sebaceous gland carcinoma of the eyelid

Twenty-one Japanese patients with sebaceous carcinoma of the eyelid were investigated for tumour incorporation of human papillomavirus (HPV) types-6, 11, 16, 18, 31, and/or 33 DNA by in situ hybridization with fluorescein isothiocyanate-labelled DNA probes, and for p53 protein accumulation by immunohistochemical analysis with an antibody to p53 protein. Thirteen tumours (61.9%), including 9 cases of multiple infections, were positive for HPV DNA. Positive signal in the nucleus was observed not only in the cancer cells, but also in the cells of surrounding normal sebaceous glands and epidermis. Positive nuclear staining of cancer cells with the antibody to p53 protein was detected in 12 cases (57.1%). p53 protein accumulation was more frequently observed in the clinically advanced cases, occasionally in association with recurrence and/or metastasis. Among the 12 p53-positive cases, 7 were also positive for the presence of HPV DNA. HPV infections exist in a high percentage of sebaceous carcinomas of the eyelid in Japan; the overexpression of p53 protein may be important in both carcinogenesis and progression.     

Expression of p53 protein related to the presence of human papillomavirus infection in precancer lesions of the larynx.

The aim of this study was to gain some insight into the relationship of human papillomavirus (HPV) infection to p53 expression and to some pathological parameters in precancerous lesions of the larynx. Formalin-fixed paraffin-embedded tissue sections containing human laryngeal precancerous lesions were screened for p53 protein by immunohistochemistry with the monoclonal antibody DO7 and for the presence of HPV infection by polymerase chain reaction with consensus primers directed against the E6 gene. The presence of p53 protein was detected in 31 of 57 specimens (54.4%) including 7 of 9 cases with mild dysplasia (78%), in 4 of 9 cases with moderate dysplasia (44%), and in 15 of 23 cases with severe dysplasia (65%). Of 16 samples with keratotic benign squamous metaplasia, 5 were also p53 positive (31%). Of 6 samples that were HPV positive, all were of type 16. Interestingly, 3 of the 6 HPV-positive samples were p53 negative. There was 1 HPV-positive case with strong p53 staining and 2 HPV-positive cases with minimal p53 staining. The 2 HPV-positive cases with minimal p53 staining had mild dysplasia. The HPV-positive case with strong p53 staining displayed severe dysplasia. Of 23 cases that were both HPV and p53 negative, 11 presented with keratosis and no dysplasia, 5 with moderate dysplasia, and 7 with severe dysplasia. Our data indicate that nuclear accumulation of p53 protein, presumably resulting from p53 gene mutation, may occur in HPV-infected epithelial tissues. On the other hand, there are many precancer lesions, some exhibiting moderate or severe dysplasia, that are both HPV negative and p53 unreactive, suggesting that alterations of genes other than the E6 oncogene and the p53 tumor suppressor gene play a role in early laryngeal carcinogenesis.     

Papillary immature metaplasia of the uterine cervix: a report of 5 cases with an emphasis on the differential diagnosis from reactive squamous metaplasia, high-grade squamous intraepithelial lesion and papillary squamous cell carcinoma.

Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.     

Correlation between human papilloma virus infection in cervical lesions and expression of p53, p21 proteins and Ki-67

BACKGROUND: Human papilloma virus (HPV) is the most important factor in the oncogenic mechanism of cervical tumor. Furthermore, in a separate multi-stage process, abnormality in cell cycle kinetics has been demonstrated. In order to elucidate the oncogenic mechanism, we examined the relationship between cervical carcinoma and HPV infection, and also investigated the expression of p53 and p21 proteins as well as the cell proliferation capability by detecting Ki-67, and analyzed the correlations of these factors. MATERIALS AND METHODS: We studied the biopsy specimens from 107 patients of chronic cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma (SCC). HPV DNA was detected by the hybrid capture method. Immunostaining by LSAB procedures were performed using antibodies to p53 protein, p21 and MIB-1. The PCR-denaturing gradient gel electrophoresis (DGGE) method was used to search for mutation in exons 5, 6, 7 and 8 of p53. RESULTS: Of 107 cases studied, high-oncogenic HPV was detected in 80 cases (74.8%) with a particularly high prevalence in SCC. No correlation was observed between HPV infection and expression of p53, p21 or Ki-67. The degree of positivity of Ki-67 expression tended to be higher with disease progression. Cases strongly positive (2+) for p53 and p21 proteins were weakly positive for Ki-67, and cases positive (1+) or negative for p53 and p21 were strongly positive for Ki-67. CONCLUSION: In oncogenesis of cervical carcinoma, p53 protein, p21 protein and HPV may act separately as independent factors in some cases, and there is a strong possibility that other factors are involved.     

Routine papillomavirus antigen staining of cervical punch biopsy specimens.

Immunocytochemical staining for papillomavirus antigen was carried out on 1147 consecutive cervical punch biopsy specimens over 12 months. Of 876 cases with cervical intraepithelial neoplasia (CIN) 351, were antigen positive and of 49 cases with histological evidence of human papillomavirus (HPV) infection but no CIN, 14 were positive. There were 204 cases reported to be normal on routine histological examination and 12 cases reported to show features suggestive but not diagnostic of HPV infection. Of the normal group, 24 (12%) were antigen positive and of the equivocal group, two were positive. In 122 of the normal or equivocal groups cytological examination was repeated at the time of colposcopy, and dyskaryosis was reported in 36. In only four cases was disease shown by HPV antigen staining when there was no diagnostic histological or cytological abnormality. HPV antigen staining assists in the recognition of the range of histological changes associated with productive HPV infection but is an insensitive test and has only limited value in supplementing histological and cytological examinations as a diagnostic aid in routine colposcopic pathology.     

HPV16,18E6蛋白与p21ras,p53在食管癌组织中表达

采用ＳＰ免疫组化法对５２例食管鳞状细胞癌和３０例食管粘膜慢性炎（对照组）进行高危ＨＰＶ１６、１８Ｅ_６和ｐ２１ｒａｓ、ｐ５３癌基因产物的检测。结果表示：鳞癌组中Ｅ_６的阳性率为６７．３１％，与对照组相比差异有极显著性（Ｐ＜０．００１），其中Ｅ_６与ｐ５３呈双阳性者为５５．７７％（２９／５２）、８９．６６％（２６／２９），显示两者阳性着色出现在部分相同区域同一癌细胞核内（似表明Ｅ_６可与ｐ５３结合形成复合物从而导致野生型ｐ５３的降解）。本组ｐ２１ｒａｓ与ｐ５３、ｐ５３与Ｅ_６的阳性表达均具相关性（Ｐ＜０．０５）。提出ＨＰＶ１６、１８感染与本地区食管癌病因学密切相关，Ｅ_６抗体是诊断ＨＰＶ１６、１８感染的良好标记。     

Immunohistochemical analysis of pleomorphic lobular carcinoma: higher expression of p53 and chromogranin and lower expression of ER and PgR

AIMS: Pleomorphic lobular carcinoma of the breast is a histological variant of infiltrating lobular carcinoma with a poor prognosis. The aim of this study is to investigate the immunohistochemical profile of this distinctive breast carcinoma in comparison with the classical type. The expression of cytokeratin, epithelial membrane antigen, gross cystic disease fluid protein-15, chromogranin, oestrogen and progesterone receptors and p53 oncoprotein was investigated to examine whether the expression of these markers correlates with the aggressiveness of this variant. METHODS AND RESULTS: Sections from 10 cases of pleomorphic lobular carcinomas were reviewed and examined for the expression of cytokeratin of high and low molecular weight, epithelial membrane antigen (EMA), gross cystic disease fluid protein-15 (GCDFP-15), chromogranin, oestrogen (ER) and progesterone receptors (PgR), and p53 oncoprotein. Immunohistochemical staining was performed on paraffin wax embedded sections. Ten cases of classical lobular carcinomas were used for comparison. A semiquantitative count of the percentage of positive tumour cells was recorded. Pleomorphic lobular carcinomas have most of the characteristic histological features of the classical type but have nuclear anaplasia and abundant granular cytoplasm. Clinically they exhibited poor prognosis and a high frequency of nodal metastases. All of the pleomorphic lobular carcinomas expressed low and high molecular weight keratin, EMA, and GCDFP-15, eight cases expressed nuclear p53 at a range between 10% and 45%. All cases expressed chromogranin (3-5%). ER and PgR were weakly positive in two cases and negative in eight cases. Classical infiltrating lobular carcinomas were all positive for cytokeratin, EMA, ER and PgR and negative for GCDFP-15. Only five cases of classical lobular carcinoma expressed p53 positivity with up to 5% nuclear staining while chromogranin showed less expression (1-2%). CONCLUSION: Pleomorphic lobular carcinoma exhibits distinct cellular features with apocrine differentiation, higher expression of chromogranin and p53 protein and lower ER and PgR in comparison with classical lobular carcinomas. Determination of p53 overexpression and reduced or absent expression of ER and PgR may help predict the behaviour of this variant of lobular carcinoma.