Utility of CK7 and CK20 immunohistochemistry in the detection of synchronous breast and colon carcinoma in a pleural effusion: a case report and supporting survey of archival material

We present a case of synchronous breast and colon carcinoma in a pleural effusion, to our knowledge the first such reported case in the English-language literature. The patient was a 55-yr-old white female with known metastatic breast and colon carcinoma who developed a malignant pleural effusion which demonstrated two strikingly different populations of malignant cells by immunohistochemical study of cell block material. One cell population demonstrated a cytokeratin (CK)7+/CK20-/ER+ phenotype, while the other demonstrated a CK7-/CK20+/ER- phenotype, consistent with breast and colon origin, respectively. An immunohistochemical survey of archival breast and colon primary and metastatic carcinomas confirmed the established CK7+/CK20- phenotype of breast and CK7-/CK20+ phenotype of colon primary carcinomas, and the maintenance of this phenotype in metastases thereof. A survey of benign and malignant mesothelial lesions confirmed the absence of staining for estrogen receptor, but showed 6/10 cases weakly positive for CK20, which has not been described in other published series. This unusual case graphically illustrates the utility of cytokeratin subset immunohistochemistry in effusion cytology.     

A renal cell carcinoma with components of both chromophobe and papillary carcinoma

We report a case of a morphologically unusual renal cell carcinoma with features of both chromophobe and papillary carcinoma. Immunohistochemical analysis of high molecular weight cytokeratins (HMWCK), cytokeratin 7 (CK7), cytokeratin 19 (CK19), c-Kit, and α-methylacyl-CoA racemase (AMACR) demonstrated differential profiles for the two components of the tumor, consistent with the respective patterns commonly observed for pure chromophobe and papillary renal cell carcinomas. Specifically, the chromophobe tumor cells expressed CK7 and c-Kit weakly, while HMWCK, CK19, and AMACR were not detectable. In contrast, the papillary tumor cells expressed uniformly HMWCK, CK7, and c-Kit and focally CK19 and AMACR. Fluorescence in situ hybridization analysis of nuclei isolated from paraffin-embedded tumor tissue detected monosomy 1, disomy 7, and monosomy 17, a common and characteristic finding in chromophobe carcinomas, in a majority of, but not all tumor cells, whereas a population characterized by disomy 1, trisomy 7, and trisomy 17, a frequent finding in papillary carcinoma, was not identifiable. Electron microscopic analysis revealed numerous characteristic small cytoplasmic vesicles in the chromophobe areas, which were absent in the papillary component. This case illustrates the rare coexistence of two distinct and admixed histologic types of renal cell carcinoma.     

Pure acinic cell carcinoma of the breast in an 80-year-old Japanese woman

Acinic cell carcinoma of the breast is an uncommon neoplasm. Since the first case of this rare variant of breast carcinoma was reported in 1996, only 10 cases have been reported in the English-language literature. Reported herein is the first case of primary acinic cell carcinoma of the breast in a Japanese woman. To the naked eye, the tumor appeared well circumscribed and the cut surface was grayish-pink and hemorrhaging. Microscopically, the tumor was predominantly made up of a monotonous proliferation of cells with a finely granular cytoplasm, resembling acinic cells of the parotid gland. Some neoplastic cells had a clear cytoplasm. In spite of extensive sampling, no common histological patterns of breast carcinoma such as in situ and invasive ductal carcinoma were recognized in the present case, indicating that the present case was pure acinic cell carcinoma. In addition, the immunohistochemical profile of this tumor was identical to that of the acinic cell carcinoma of the salivary gland: estrogen receptor, progesterone receptor, HER2 and cytokeratin (CK)20 were negative and amylase and CK7 were positive. The patient has been well for 22 months since the wide local excision of the tumor and no signs of salivary neoplasm are evident to date.     

Clear cell variant of squamous cell carcinoma originating in the esophagus: report of a case with immunohistochemical and oncogenetic analyses

The cutaneous clear cell squamous cell carcinoma (SCC) is a rare tumor thought to be associated with hair follicle or skin appendage differentiation. We report herein a rare variant case of a clear cell SCC originating in the esophagus. A 70-year-old Japanese man was found to have a tumor in the esophagus. The excised neoplasm showed dominance of clear cell over conventional SCC components; the two components in an apparent continuum. The clear cells, regular in size with a moderate nuclear/cytoplasmic ratio and relatively hyperchromatic and centrally located nuclei, were compactly arranged in sheets. Glycogen deposition was apparent on PAS staining with or without diastase digestion and under the electron microscope. The clear cell SCC components were positive for cytokeratin (CK)7, CK8, CK18 and CK19, but were negative for CK5/6 or CK14. Reciprocal staining patterns of CKs were apparent in conventional SCC components. The present case and cutaneous clear cell SCC counterparts share some histopathologic characteristics whereas CKs expression differs between the two. Overexpression of p53 protein, without evidence of any mutation, and reduced p16(INK4a) were noted in both clear cell and conventional SCC components. No mutations of Kras, BRAF or β-catenin genes were found in both tumor components.     

p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer

AIMS: To study the expression of p63, cytokeratin (CK) 5 and CK8/18 in invasive ductal carcinomas and their relationship with BRCA1 and other pathological and immunohistochemical features of clinical significance. METHODS AND RESULTS: Immunohistochemistry with the antibodies p63, CK5, CK8/18, BRCA1, oestrogen receptor, progesterone receptor, p53, c-erbB-2 and Ki67 was performed in 102 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. The CK5+ cases were submitted to a double-immunolabelling study with p63. There was a strong relationship between CK5 and p63 expression and both markers were associated with hormonal receptor-negative high-grade carcinomas with high proliferative rate. Furthermore, there was coexpression of CK5 and p63 in neoplastic cells, indicating that p63, like CK5, is a marker of the basal phenotype of breast cancer. There was a strong relationship between reduced expression of BRCA1 with both p63 and CK5 expression as well as an inverse correlation between p63 and CK8/18 expression, suggesting that loss of p63 expression is required for the transition between a basal to a luminal phenotype of breast carcinoma. CONCLUSIONS: Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.     

Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast

Previously, we showed that pure ductal carcinoma in situ (DCIS) of the breast can be divided into 3 subtypes (luminal, basal/stem, and null) based on the expression of 5 cytokeratin (CK) markers: CK5/6, CK14, CK17 (stem/basal), and CK8, CK18 (luminal). The distributions of CK subtypes were associated with nuclear grade and differential expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (EGFR). In this study, we further explore the expression patterns of CK markers, ER-alpha, PR, HER-2/neu, and EGFR by immunohistochemical (IHC) analysis of 99 cases of pure DCIS and 96 cases of DCIS with co-existing invasive ductal carcinoma (DCIS/IDC). We show that between high-grade DCIS and DCIS/IDC, there are differential expression patterns for ER-alpha, PR, and EGFR in corresponding CK subtypes, suggesting that at least some pure DCIS is molecularly distinct from DCIS/IDC. In most cases there is a high degree of co-expression of these markers between DCIS and the co-existing IDC, suggesting that DCIS is frequently a precursor lesion for co-existing IDC. The rate of discordant expression of these markers is low and is more frequently associated with high-grade carcinoma, suggesting that other molecular pathways also may also be present. There are significant differences in the expression of these molecular markers between high-grade and non-high-grade carcinomas, supporting the view that high-grade and non-high-grade carcinomas of the breast are molecularly distinct entities.     

Bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative breast carcinomas

Bone is one of the most common sites of distant metastasis for breast carcinomas. In this study, our objective is to identify molecular markers and molecular subtypes that may predict patients at higher risk of developing bone metastasis. Immunohistochemical analysis with antibodies against estrogen receptor α, progesterone receptor, androgen receptor, Her2/neu, epidermal growth factor receptor, CK5/6, CK14, CK17, CK8, and CK18 was performed on representative sections of 21 breast carcinomas with bone metastasis and 94 cases without bone metastasis. The expression rates of receptors, subtype distributions (basal versus nonbasal) of 3 molecular classifications (cytokeratin, triple negative, and cytokeratin/triple negative), and 5 subtypes of cytokeratin/triple negative classification were compared between these 2 groups. We found that (1) the breast cancers with bone metastasis were associated with a significant percentage of estrogen receptor–positive/progesterone receptor–negative tumors compared with tumors without bone metastasis (38% versus 6%, P < .0001). (2) There was significant difference on estrogen receptor expression between high grade and non–high grade in tumors with or without bone metastasis (P = .0084 and 1.0000, respectively). (3) The breast cancers with bone metastasis were more likely to be estrogen receptor positive (85%) and androgen receptor positive (95%) compared with those without bone metastasis (59% and 74%, respectively, both P < .05). (4) There was no significant difference between tumors with or without bone metastasis in subtype distribution (basal versus nonbasal) among all 3 molecular classifications. (5) Luminal B carcinomas of cytokeratin/triple negative classification tended to be associated with bone metastasis but not to a statistically significant extent. In conclusion, bone metastasis is strongly associated with estrogen receptor–positive/progesterone receptor–negative tumors. Significant difference in estrogen receptor expression between high-grade and non–high-grade tumors with bone metastasis suggests that different panels of molecular markers should be used to predict bone metastasis in these 2 groups of tumors.     

Cytokeratin profiles of male breast cancers

AIMS: The prognostic factors and expression of molecular markers in male breast carcinomas are similar to those in female breast cancers. The identification of distinct cytokeratin (CK) profiles (basal as opposed to luminal cells) helps to identify subsets of tumours with different clinical behaviour. The aim of this study was to investigate CK expression in male breast cancer. METHODS AND RESULTS: Thirty-two cases of male breast cancer were studied. The panel of CKs studied by immunohistochemistry included: 5/6, 14, 17, 18 and 19. Pathological findings and CK expression were analysed in all cases. Histological patterns included ductal carcinoma in situ, invasive ductal carcinoma and mixed patterns. Four cases were positive for CK5/6 and CK14, identifying a basal-like phenotype. CK17 was negative in all but two cases. All cases expressing either CK5/6 or CK14 were invasive carcinomas of high nuclear and histological grade and were also larger compared with the tumours not expressing CK5/6 and CK14. All tumours except three (also negative for CK5/6) expressed CK18 and CK19. The four basal-like tumours were negative for Her-2 expression. CONCLUSIONS: Male breast carcinomas have a basal-like phenotype that is similar in frequency to that of female breast carcinomas. The expression of CK5/6 and CK14 identifies a subset of pathologically aggressive male breast cancers.     

Cribriform-morular variant of papillary carcinoma: the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma. A case report with clinical and molecular genetic correlation

The increased incidence of thyroid carcinomas in familial adenomatous polyposis (FAP) patients is well recognised. These thyroid neoplasms display distinctive clinicopathological features and generally show good prognostic outcome. Recently, unusual sporadic tumours that share the morphological features of FAP-associated thyroid carcinomas have also been described. In this report, we document a case of a thyroid tumour in a previously well, 46-year-old female. Histology revealed a circumscribed neoplasm composed of tubular, papillary, cribriform and solid areas. The pseudostratified columnar tumour cells showed occasional nuclear grooves and rare nuclear inclusions. Immunohistochemistry showed positive staining with antibodies to cytokeratin AE1/AE3, oestrogen and progesterone receptor proteins. Focal immunoreactivity was also noted with antibodies to thyroglobulin, epithelial membrane antigen, 34betaE12 and cytokeratin CK7. The absence of polyps on colonoscopy and germline mutation in the adenomatous polyposis coli (APC) gene provides evidence that this tumour represents the sporadic counterpart of FAP-associated thyroid carcinoma. The patient is well with no evidence of disease 7 months following resection of the tumour. The differential diagnoses and molecular genetics of this unusual tumour are discussed.     

Clear cell papillary renal cell carcinoma with characteristic morphology and immunohistochemical staining pattern

Clear cell papillary renal cell carcinoma is newly-defined entity initially believed to be associated with end stage renal disease. We report a rare case of this neoplasm in a 70-year-old female patient with no known history of end-stage renal disease who presented with haematuria lasting several days. After initial workup, a computed tomography (CT) scan was performed and revealed a cystic mass in the right kidney. Material obtained by fine needle aspiration (FNA) biopsy of the mass was felt to be suspicious for renal cell carcinoma. The patient subsequently underwent right nephrectomy, and the lesional tissue was examined microscopically. A 2.3 cm in greatest dimension cystic space circumscribed by a fibrous wall was surfaced by a single layer of bland cuboidal cells with abundant clear cytoplasm. The solid component of the tumour consisted of branching papillae with delicate fibrovascular cores and uniformly lined by cells similar to those of the inner wall of the cyst. Some of the fibrovascular cores were markedly expanded by a myxoid-appearing substance, but no foamy cells were appreciated. Immunohistochemically, the neoplastic cells were diffusely immunoreactive with cytokeratin 7 (CK7), epithelial membrane antigen (EMA), high molecular weight cytokeratin (HMWCK) and vimentin. Neoplastic cells were only focally immunoreactive with CD10, and were negative for both p63 and alpha-methylacyl-CoA racemase (AMACR) (P504S). The cytomorphological features and immunohistochemical staining pattern of this tumour was consistent with that of clear cell papillary renal cell carcinoma (CCPRCC), as described by Gobbo et al.     

Cytokeratin typing as an aid in the differential diagnosis of primary versus metastatic lung carcinomas, and comparison with normal lung

Due to more efficient chemotherapy protocols, the number of second and even third primary carcinomas is steadily increasing. To denominate the possible origin of a carcinoma, different markers are available as an aid, e.g. hormones, proteins and lipoproteins, secretion products and cytoskeletal proteins. Cytokeratins (CKs) have gained new popularity; however, they have not been extensively evaluated in lung tumours. In our study we evaluated the staining patterns of CK polypeptides 4-8, 10, 13, 14, and 17-20 and high molecular weight (HMW) CK polypeptides in routinely processed primary lung carcinomas and lung metastases of diverse origin. As expected, immunohistochemical investigation gave no clear-cut results, but, with statistical analysis, lung adenocarcinomas could be separated from metastatic adenocarcinomas using CK 5 and 18 and HMW CK (specificity 92.5%, sensitivity 62.5%). The different origin of the metastases could often be detected using CK 18 and CK 20. Lung clear cell carcinomas and large cell carcinomas with clear cell areas could be distinguished from metastatic renal clear cell carcinomas by the CK 7 staining reaction. Squamous cell carcinomas of the lung and metastatic squamous cell carcinomas of the larynx, pharynx and oesophagus could not reliably be separated in part due to the few number of cases available. CK polypeptide typing is thus an additional aid in the differential diagnosis of lung carcinomas versus carcinomas metastatic to the lung.     

Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases.

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.     

Mesothelial markers in high-grade breast carcinoma

Duhig E E, Kalpakos L, Yang I A & Clarke B E
(2011) Histopathology 59 , 957–964 Mesothelial markers in high‐grade breast carcinoma Aims: Advances in molecular profiling have subdivided breast carcinomas into distinct subtypes. Basal carcinomas are generally oestrogen receptor (ER)?progesterone receptor (PR)?/human epidermal growth factor receptor 2 (HER2)?, and cytokeratin (CK)5/6+. This profile overlaps with that of mesothelial cells. This study of high‐grade breast carcinomas was undertaken to determine the expression of mesothelial markers. Methods and results: Immunohistochemistry was performed on 23 basal‐like breast carcinomas and 30 high‐grade breast carcinomas with variable ER, PR and HER2 expression. The incidence of staining of CK5/6, CK14, calretinin, Wilms’ tumour 1 (WT1), thrombomodulin and epithelial membrane antigen was assessed statistically. CK14 staining was more specifically associated with triple‐negative tumours than CK5/6. Calretinin positivity was statistically associated with basal‐like carcinomas. WT1 and thrombomodulin expression was infrequent and limited to a small number of non‐basal carcinomas. Conclusions: There is an overlap between the immunophenotype of mesothelial cells and that of basal‐like carcinomas of breast. Positive calretinin and CK5/6 are not specific, and may be seen in both mesothelial cells and basal‐like breast carcinomas. Negative ER and PR of basal carcinomas may also bias the observer against a breast origin. However, other negative mesothelial markers, such as WT1 and thrombomodulin, may help point to the correct diagnosis.     

Immunohistochemical distinction of human carcinomas by cytokeratin typing with monoclonal antibodies.

Carcinomas of different origin have been tested in immunofluorescence microscopy with the monoclonal murine antibodies CK1-CK4, which recognize a single cytokeratin polypeptide (human cytokeratin No. 18) present in simple but not in stratified squamous epithelia, and with the monoclonal antibody KG8.13 and guinea pig kerA antibodies, both of which recognize a variety of cytokeratins common to almost all epithelial cell types. Tumors derived from simple epithelia, including adenocarcinomas and some other tumors such as ductal breast carcinomas, were strongly stained by all three antibodies. So was a transitional carcinoma of the bladder. In contrast, basal cell epithelioma, cloacogenic carcinoma, and squamous cell carcinoma of skin, tongue, and esophagus appeared negative with CK1-CK4 but positive with the other two antibodies. Other squamous cell carcinomas derived from epiglottis and cervix uteri showed a mixture of positive and negative cells when tested with CK1-CK4, although all tumor cells were positive when tested with KG8.13 and with kerA. Thus, use of an appropriate collection of cytokeratin antibodies with different specificities not only allows tumors of epithelial origin to be distinguished from other tumor types but, in addition, allows a further subdivision of carcinomas in relation to their histologic origin.     

p63, CK7, PAX8 and INI-1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high-grade tumours of the renal collecting system

Carvalho J C, Thomas D G, McHugh J B, Shah R B & Kunju L P
(2012) Histopathology  60, 597–608
p63, CK7, PAX8 and INI‐1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high‐grade tumours of the renal collecting system Aims: High‐grade, poorly differentiated, infiltrative carcinomas involving the renal sinus region often pose challenging differential diagnostic considerations, specifically differentiation of urothelial carcinoma (UC) from renal cell carcinoma (RCC) subtypes. Accurate classification, especially the distinction of UC from RCC, is critical, as therapeutic approaches differ. Methods and results: Cluster analysis was performed on immunohistochemical data from 18 invasive UCs, six CDCs, two RMCs, 18 type 2 papillary renal cell carcinomas (PRCCs) and 20 high‐grade clear cell renal cell carcinomas (CRCCs) using a broad panel of traditional and novel immunohistochemical markers. The initial analysis with all antibodies segregates almost all the RCCs (45 of 46, 98%) from all the UCs based on the lack of expression of p63 in all (100%) RCCs, along with predominant strong expression of paired box gene 8 (PAX8) and vimentin, predominant lack of expression of high molecular weight cytokeratin (HMCK) and CK7 and variable expression of RCC, CD10, CA1X and PAX2. All the UCs cluster together with strong, diffuse reactivity for p63, predominant reactivity for CK7 and high molecular weight kininogen (HMWK), and absent to minimal staining with PAX8, RCC antigen, PAX2, alpha‐methylacyl‐CoA racemase (AMACR), carbonic anhydrase IX (CAIX) and vimentin. After removing antibodies with significant overlap and/or minimal impact, a second analysis with a limited panel including p63, CK7, vimentin, integrase interactor 1 (INI‐1) and PAX8 was performed. Again, the majority of UCs cluster into one group and p63 positivity separates all UCs from RCCs. Conclusions: Lack of INI‐1 expression, noted exclusively in RMCs, segregates RMCs into a separate cluster. PAX8 is rarely positive (17%) in UC, is commonly expressed in CDC, RMC, PRCC and CRCC and is superior to PAX2.     

Increased alpha-B-crystallin expression in mammary metaplastic carcinomas

Chan S‐K, Lui P C W, Tan P‐H, Yamaguchi R, Moriya T, Yu A M C, Shao M‐M, Hliang T, Wong S‐I & Tse G M
(2011) Histopathology 59 , 247–255 Increased alpha‐B‐crystallin expression in mammary metaplastic carcinomas Aims: Mammary metaplastic carcinoma is a rare breast carcinoma, and may present diagnostic difficulty. Alpha‐B‐crystallin has been recently reported to be expressed in basal‐like and metaplastic carcinomas. Methods and results: Thirty‐three metaplastic carcinomas, 44 conventional high‐grade carcinomas and 28 mesenchymal spindle cell neoplasms as controls were assessed for their expression of αB‐crystallin and conventional basal‐like phenotypic markers CK5/6, CK14, p63, c‐kit and epidermal growth factor receptor (EGFR) by immunohistochemistry. Alpha‐B‐crystallin staining was positive in 68% of the metaplastic carcinomas with cytoplasmic staining in all tumour cell components. CK5/6, CK14, p63, c‐kit and EGFR stained 43%, 68%, 45%, 21% and 25% of the metaplastic carcinomas, respectively. Combining these markers, 84% of the metaplastic carcinomas expressed either αB‐crystallin or CK14. In comparison, only 14% (six cases) of conventional high‐grade carcinoma and 7% (two cases) of mesenchymal spindle cell neoplasm expressed αB‐crystallin; all but one of these carcinomas were ER/PR/HER2 triple‐negative. Conclusions: Using αB‐crystallin for diagnosis of metaplastic carcinoma gives a 68% sensitivity, 88% specificity, 74% positive predictive value, 85% negative predictive value and 78% accuracy. The sensitivity is enhanced to 84% with combinations of αB‐crystallin/CK14. Alpha‐B‐crystallin may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.     

Spindle cell carcinoma progressed from transitional cell carcinoma of the urinary bladder

The author reports a very rare case of spindle cell carcinoma (SpCC) of the urinary bladder progressed from ordinary papillary transitional cell carcinoma (TCC). A 63-year-old man complained of hematuria. A transurethral endoscopic examination revealed a papillary tumor, and transuthetral resection of bladder tumor (TUR-BT) was performed and was diagnosed as ordinary papillary urothelial TCC. Since then, he was treated with TUR-BT eight times. Chemotherapy, radiation, radical cystectomy and lymph nodes dissection were performed 16 years after the first TUR-BT. However, he developed rectal mucosal metastasis. He is now alive 17 years after the first presentation. All the TUR-BT specimens were ordinary papillary TCCs without invasion (pTa). Immunohistochemically, the TUR-BT specimens were positive for pancytokeratin, high molecular weight cytokeratin (CK), CK 5/6, CK 7, CK 18, CK 19, CK 20, p53, p63, Ki-67 (10%), and negative for other antigens examined including vimentin. The cystectomy bladder specimens show broad ulcers and polypoid lesions, and malignant spindle cells (SpCC) invading into muscular layer were present. No TCC elements were recognized. The tumor cells were positive strongly for vimentin, and less strongly for pancytokeratin, high molecular weight cytokeratin, CK 5/6, CK 14, CK 18, p53, p63 and Ki-67 (95%), and negative for other antigens examined. The rectal metastatic lesion showed SpCC without TCC elements, and were strongly positive for vimentin, and weakly positive for pancytokeratin, S100 protein, p53, p63, Ki-67 (90%), neuron-specific enolase, CD56, KIT and PDGFRA. It was negative for other antigen examined. It is strongly suggested that the present SpCC were progressed from ordinary TCC.     

The cytokeratin profile of medullary carcinoma of the breast

AIMS: The cytokeratin (CK) phenotype and vimentin expression of 31 medullary carcinomas was studied using commercially available antibodies on archived material. Comparing the phenotype of typical and atypical tumours and the phenotype of metastases, the biological significance of cytokeratin and vimentin expression in medullary carcinomas of the breast was determined. METHODS AND RESULTS: Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to vimentin were used. All the typical and atypical medullary carcinomas and the metastases (10 cases) stained negatively for CK4 and positively for CK8-18 (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative. Twelve per cent of the tumours contained CK14. Twenty-five per cent of the typical, 43% of the atypical and 20% of the metastatic medullary carcinomas showed CK5-6 positivity. No association between the cytokeratin-vimentin profile of the tumours and axillary node metastases, tumour size or oestrogen receptor status was found but instability of CK expression was demonstrated by comparing the primary tumours with their metastases. CONCLUSIONS: : Medullary carcinomas of the breast express all the glandular type CKs including CK19 and additionally a proportion of the tumours expresses some of the CKs typical for myoepithelial cells. There was no correlation with prognostic factors.     

Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours

AIMS: The tissue distribution of cytokeratin 14 (CK14) in epithelial neoplasms is not well defined. We have evaluated 435 cases of epithelial neoplasm of various origins with cytokeratin 14 monoclonal antibody with special attention to possible use in differential diagnosis. METHODS AND RESULTS: Immunohistochemistry (ABC-HRP method) was performed for detection of CK14. We found that the expression of cytokeratin 14 was generally restricted to: (i) the majority of cases of squamous cell carcinoma regardless of origin (67/74) and degree of differentiation; (ii) neoplasms with focal squamous differentiation, including endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid Hurthle cell adenoma (1/1) and salivary gland Warthin's tumour (2/2). CONCLUSION: CK14 protein is a useful marker in differential diagnosis of squamous cell carcinomas.