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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 13  |  Issue : 2  |  Page : 73-82

The diagnostic utility of pan-cytokeratin, CK19, CEA, CD10, and p63 in differentiating clear cell odontogenic carcinoma from hyalinizing clear cell carcinoma


Department of Oral Pathology, Faculty of Dentistry, Tanta University, Tanta, Egypt

Date of Submission08-Mar-2016
Date of Acceptance15-Apr-2016
Date of Web Publication23-Aug-2016

Correspondence Address:
Omneya M Wahba
Department of Oral Pathology, Faculty of Dentistry, Tanta University, Tanta
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-8574.188907

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  Abstract 


Background
Clear cell carcinoma (CCC), or hyalinizing CCC, and clear cell odontogenic carcinoma (CCOC) are rare and typically indolent malignancies that can be diagnostically challenging.
Aim
The aim of this study was to determine the diagnostic utility of p63, carcinoembryonic antigen (CEA), CD10, pan-cytokeratin (pan-CK), and cytokeratin 19 (CK19) in the diagnosis of CCOC and hyalinizing CCC.
Material and Methods
The study groups comprised patients with CCOC (n = 15) and CCC (n = 10). The blocks of CCOC and CCCs were prepared for immunohistochemical staining for p63, CEA, CD10, pan-CK, and CK19.
Results
The results of this study revealed significant differences between the expression of pan-CK, CK19, and CEA between CCOC and hyalinizing CCC, with no significant value of p63 and CD10 expression. In conclusion, CCOC and hyalinizing CCC are malignant, locally aggressive tumors with the capacity to metastasize.
Conclusion
Based on the current observations and immunostains, it can be concluded that they are difficult, and, in some cases, impossible to distinguish morphologically and immunohistochemically despite a different cell of origin. Pan-CK, CK19, and CEA may have slight significant difference between CCOC and hyalinizing CCC but the diagnosis of these tumors mainly depends on the exclusion of other tumors. In addition, histological and immunohistochemical analyses of neoplasm features have limited value.

Keywords: clear cell carcinoma, clear cell odontogenic carcinoma, pan-cytokeratin


How to cite this article:
Wahba OM. The diagnostic utility of pan-cytokeratin, CK19, CEA, CD10, and p63 in differentiating clear cell odontogenic carcinoma from hyalinizing clear cell carcinoma. Tanta Dent J 2016;13:73-82

How to cite this URL:
Wahba OM. The diagnostic utility of pan-cytokeratin, CK19, CEA, CD10, and p63 in differentiating clear cell odontogenic carcinoma from hyalinizing clear cell carcinoma. Tanta Dent J [serial online] 2016 [cited 2017 Oct 22];13:73-82. Available from: http://www.tmj.eg.net/text.asp?2016/13/2/73/188907




  Introduction Top


Clear cells may be found in many tumor types. They are a result of fixation defects, intracellular storage of some substances (such as glycogen, lipid, mucin), or paucity of organelles[1]. In the head and neck region, clear cell tumors usually are odontogenic [2] or salivary in origin, although metastatic tumors need to be considered [3].

Odontogenic neoplasms, which are composed predominantly of clear cells, are almost rare [4]. Examples include the clear cell subtype of Pindborg tumor (calcifying epithelial odontogenic tumor)[5],[6] and of ameloblastoma [7],[8],[9] and clear cell odontogenic carcinoma (CCOC) [10]. The latter has a high rate of recurrence and tendency to metastasize to regional nodes and distant sites [11].

CCOC is considered a rare odontogenic tumor associated with aggressive clinical behavior, metastasis, and low survival rate. CCOCs were called clear cell ameloblastoma or clear cell odontogenic tumors and were considered benign in the WHO classification [12]. Because these tumors have an aggressive behavior and may metastasize to lymph node and distant organs, the 2005 WHO classification classified them as carcinomas characterized by sheets and islands of vacuolated and clear cells [13].

Clear cell carcinoma (CCC) is a malignancy that arises from the salivary glands, especially within the palate, the tongue, the hypopharynx, nasopharynx, subglottic larynx, parotid, and lacrimal gland [14],[15],[16],[17]. Although CCC is considered a low-grade malignant tumor, 25% of its patients have been reported to have metastases and 12% have local recurrence [15],[16]. Metastases usually involve the lung, bones, and the regional lymph nodes [18].

p63 is considered a member of the p53 family. During early development of embryo, it is important for the specialization of several epithelia [19]. The p63-deficient mice are characterized by abnormalities of stratified squamous epithelia and their derivatives, including sebaceous, salivary, and mammary glands, and defects in the craniofacial structures and limbs. Thus, it has been concluded that p63 plays a key role in regulating epithelial proliferation and differentiation processes [20],[21].

In addition, p63 expression may be used as a special marker for some epithelial progenitor cells in the esophagus, including mucosal gland ducts [22]. In a recent study, p63 protein has been detected in some human normal tissues: breast, larynx, bladder, kidney esophagus, tonsil, lung, and skin [23]. Furthermore, p63 is considered a selective nuclear marker of the myoepithelial cells in the human breast tissue, as shown by Barbareschi et al. [24].

p63 is not a classical tumor-suppressor gene [25]. Several researchers have demonstrated high levels of p63 protein in squamous cell carcinomas of the gastrointestinal tract [26]. p63 expression has also been observed through immunohistochemistry in lung, skin, and cervical squamous cell carcinomas [27]. In addition, by screening a large number and variety of neoplasms, Di Como et al. [28] have detected p63 protein in non-Hodgkin lymphomas urothelial carcinomas and thymomas. They found p63 expression in four pleomorphic adenomas and two of the four carcinomas of the salivary glands.

Carcinoembryonic antigen (CEA) is considered as a sum of related glycoproteins involved in cell–cell adhesion. CEA is normally produced during fetal development in the gastrointestinal tissue, but the production stops just before birth. Therefore, CEA is usually present only at low levels in the blood of healthy persons. However, the serum levels are also raised in some types of cancer, which means that it may be used as a tumor marker in clinical tests [29].

Serum CEA measurements in patient with colorectal cancer is useful in the management [30],[31]. In addition, CEA has been evaluated in some types of malignancies, including breast cancer [32]. In their study, Kochi et al. [33] concluded that high levels of CEA provide additional prognostic value in patients with primary gastric cancer.

CD10 (common acute lymphoblastic leukemia or neutral) is a cell surface glycoprotein present in a variety of healthy cells and, acting as an enzyme, can hydrolyze peptide bonds, thus decreasing the cellular response to local peptide hormones. CD10 is strongly and diffusely expressed by clear cells in healthy kidney and in renal cell carcinoma [34].

CD10 is expressed in different types of cancers, cutaneous neoplasms [35], mesotheliomas [36], hemangioendotheliomas [37], ovarian carcinomas [38], urothelial carcinomas, prostatic adenocarcinomas, pancreatic adenocarcinomas, colonic adenocarcinomas, melanomas, spindle cell sarcomas, ovarian carcinomas, hepatocellular carcinomas, endometrial stromal sarcomas, lung carcinomas, and pancreatic solid pseudopapillary tumors [39].

Cytokeratins (CKs) are intermediate filaments: type I and type II [40],[41]. In their study, Moll et al. [42] classified 19 human epithelial keratins with different molecular weights within the 40–70 kDa range, and an additional keratin was identified, CK20. They can be classified according to their molecular weights (low and high), and as acidic or basic. Pan-cytokeratin (pan-CK), which is a blend of CK, is common to most epithelial tissues but not all of them, and is characterized by the antibody AE1/AE3 [40]. CK19 is type I keratin; it is the smallest one and it is exceptional because it lacks the typical domain (no α helix) [42]. It is expressed in most simple epithelia: ductal, intestinal, gastric epithelia, and in the mesothelium. Moreover, it is present in urothelial cells, nonkeratinized stratified squamous epithelium, and pseudostratified epithelia [43].

In thyroid pathology, CK19 can facilitate the differential diagnosis between papillary carcinoma with strong and diffuse staining and other thyroid cancers with weak and focal staining [43]. CK19 is detected in the epithelium near squamous cells carcinomas, which suggests that it could be used as a fundamental biological agent of the malignant progression [44].

Given the changes in the expression of CK19 in the inner enamel epithelium, some researchers have suggested that CK19 could be considered as an effective marker of ameloblast differentiation [45].

These considerable histologic similarities may result in difficulty in differentiating CCC from CCOC in the maxillary or mandibular region. Adding, the description of a 'central hyalinizing clear cell carcinoma' involving the jawbones on the basis of histologic criteria. Finally, the importance of this distinction is not particularly clear at this point. In a recent study, a comparison was carried out between the immunohistochemical profile of CCC and that of CCOC in an attempt to resolve this diagnostic challenge.

The aim of this study was to determine the diagnostic utility of p63, CEA, CD10, pan-CK, and CK19 in the diagnosis of CCOC and hyalinizing CCC.


  Materials and Methods Top


A total of 25 cases were used in this study, including the diagnosed cases that were retrieved from archives of the Department of Oral Pathology, Faculty of Dentistry, Tanta University. The study groups comprised patients with CCOC (n = 15) and CCC (n = 10).

To confirm the diagnosis of the samples in the study, first, 5 μm sections were prepared and were stained using the hematoxylin and eosin staining protocol. The diagnosis was then confirmed by two pathologists. Sections with sufficient tissue with proper fixation were selected, and those with inflammation and hemorrhage, insufficient tissue, and incisional biopsy were excluded from the study. Afterward, the blocks of CCOC and CCC were prepared for immunohistochemical staining for p63, CEA, CD10, pan-CK, and CK19.

Immunohistochemistry

For immunohistochemical staining, 4 μm sections were prepared from each paraffin block and were deparaffinized in the xylene solution and then dehydrated in a graded alcohol series. To block the internal peroxidase activity, hydrogen peroxide (3%) in a phosphate buffer solution was used. Then, antigen retrieval was carried out in a microwave oven (Panasonic 1380W, USA) for 10 minutes, under the pressure of almost 2 atm at 120°C. Further incubations using prediluted ready-to-use primary mouse monoclonal antibody anti-p63 (clone 4A4; Sigma-Aldrich Inc., USA), 2 mg/ml; anti-CEA (Biocare Medical, Concord, California, USA), dilution 1: 200; anti-CD10 (Dako, Denmark, USA) dilution 1: 40; pan-CK (AE1/AE3) (Biocare Medical), 10 mg/ml; and anti-human CK19 (Dako), dilution 1: 50 were used as the primary antibodies for 30 min and were incubated in a moist chamber in room temperature for 1 day, followed by the application of secondary antibody (for 15 min), DAB (producing brown staining), and Meyer's hematoxylin (for background staining). The samples were placed in PBS immediately after each of the above-mentioned steps. Prostate, small intestine, kidney, skin, and thyroid gland, respectively, were positive according to the manufacturer's instructions. The negative control was prepared by the replacement of primary antibody with PBS.

Assessment of immunohistochemistry stained sections

Presence of brown-colored reaction nuclear (p63), membranous (CD10) or cytoplasmic (CEA, pan-CK and CK19), was considered as positive reaction. The assessment of intensity of the immunostaining was classified as negative (no tumor cells showed positivity), weak (less than 25% of tumor cells showed positivity), moderate (25–50% of tumor cells were positive), or strong (more than 50% of tumor cells were positive) from three fields using a blinded analysis obtained by two independent pathologists using a conventional diagnostic microscope (Eclipse 80i; Nikon, Tokyo, Japan), and a further image analysis was carried out by using the Image J software, version 4.10.03 (Nikon).

Statistical analysis

For statistical analysis, all measured data were expressed as mean±SD. All statistical analyses were performed using the one-way analysis of variance followed by Dunnett's post-hoc test to reveal the statistical significance of the difference. Values of P less than 0.05 indicated a statistically significant difference.


  Results Top


Histopathological findings

CCOC revealed sheets or nests of different sized epithelial cells with clear eosinophilic cytoplasm separated with fibrovascular septa ([Figure 1]). The cells adjacent to the fibrovascular septa were cuboidal or columnar, showing high nuclear/cytoplasmic ratio and eosinophilic cytoplasm, whereas those in the center of the nests were larger and polygonal, with abundant clear cytoplasm ([Figure 2]). Each cell had a single nucleus with fine chromatin and prominent eosinophilic nucleolus. The cells at the periphery occasionally demonstrated nuclear palisading away from the basement membrane, i.e., reverse nuclear polarity. These peripheral cells also showed occasional mitoses. Dense strands of hyalinized connective tissue separated the clear cell nests. Presence of small cords of hyperchromatic basaloid epithelial cells in-between the hyalinized stroma.
Figure 1: Hematoxylin and eosin-stained tissue sections showing nests of clear cells separated by fibrovascular septa (original magnification: ×100).

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Figure 2: Hematoxylin and eosin-stained tissue sections showing large polygonal cells with abundant clear cytoplasm (original magnification: ×200).

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CCC showed nearby similarity to CCOC. Histologically, all tumors were predominantly composed of round or polygonal cells with cytoplasmic clearing arranged in various combinations of solid, nested, and infiltrative patterns ([Figure 3]). Admixed with the clear cells, there were cells with granular eosinophillic cytoplasm ([Figure 4]). Some nests were separated by hyalinized fibrous septa. Pleomorphism was occasionally apparent, but mitoses were rare; only 10% of the cases showed increased mitotic activity.
Figure 3: Hematoxylin and eosin-stained tissue sections showing diffuse infiltration of clear cells (original magnification: ×100).

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Figure 4: Hematoxylin and eosin-stained tissue sections showing pleomorphism and hyperchromatism of clear cells (original magnification: ×200).

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Immunoprofile of clear cell odontogenic carcinoma

All the stained tumors were positive for pan-CK. Strong cytoplasmic staining was seen within the nests of clear cells in CCOC ([Figure 5]a and [Figure 5]b), moderate nuclear staining was seen for the clear cells of CCOC to p63 ([Figure 5]c and [Figure 5]d), and weak cytoplasmic staining was seen for the clear cells of CCOC to CK19 and CEA ([Figure 5]e and [Figure 5]f, respectively). In addition, weak to negative membranous staining was seen for the clear cells of CCOC to CD10 ([Figure 5]g and [Figure 5]h).
Figure 5: Immunoprofile of CCOC: (a) Pan-cytokeratin; (b) pan-cytokeratin; (c) p63; (d) p63; (e) cytokeratin 19; (f) carcinoembryonic antigen; (g) CD10; (h) CD10. Original magnification: ×100. CCOC, clear cell odontogenic carcinoma.

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Immunoprofile of clear cell carcinoma

There was a moderate staining to pan-CK for clear cells in CCC ([Figure 6]a), and strong to moderate nuclear staining was seen for clear cells of CCC to p63 ([Figure 6]b). Some clear cells showed weak cytoplasmic staining against p63 ([Figure 6]c). Furthermore, there was a negative staining to CK19 CEA and CD10 ([Figure 6]d,[Figure 6]e,[Figure 6]f).
Figure 6: Immunoprofile of CCC: (a) Pan-cytokeratin; (b) p63; (c) p63; (d) cytokeratin 19; (e) carcinoembryonic antigen; (f) CD10. Original magnification: ×100. CCC, clear cell carcinoma.

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Statistical results

Statistical analysis of pan-CK, p63, CK19, CEA, and CD10 between CCOC and CCC is illustrated in [Figure 7].
Figure 7: Histogram showing mean values of area percentage of expression of pan-cytokeratin, p63, CK19, CEA, and CD10 in CCOC and CCC. CCC, clear cell carcinoma; CCOC, clear cell odontogenic carcinoma; CEA, carcinoembryonic antigen; CK, cytokeratin.

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From the results of the statistical analysis, a significant difference was found between CCOC and CCC as regards pan-CK (P = 0.009), CK19 (P = 0.036), and CEA (P = 0.011). But the expressions of p63 and CD10 in CCOC and CCC were not significant (P = 0.646 and 0.524, respectively).


  Discussion Top


This study was carried out to elucidate the diagnostic challenge between CCC and CCOC via the immunohustochemical expression of pan-CK, CK19, CEA, p63, and CD10.

Clear cell transdifferentiation is not restricted to a certain type of tumor. The presence of palisading cells may support the odontogenic nature of such lesions, especially when accompanied by inductive fibrohyalinization of the stroma. But still, CCC and CCOC show such a degree of histopathological overlap that makes distinction impossible [13].

In the present study, all cases of CCOC showed strong to moderate nuclear staining to p63, which was in agreement with the results obtained by Signoretti et al. [46], who found that the expression of p63 in myoepithelial and basal epithelial cells has a diagnostic value, and p63 could be used to verify or to exclude invasion in breast and prostate carcinomas.

p63 is not considered a classical tumor-suppressor gene. The data are most consistent with supporting the concept that ΔNp63 isoforms have oncogenic properties, but that TAp63 isoforms have tumor-suppressive properties [46]. In the present study, ΔNp63 isoforms showed oncogenic properties as the p63 expression was increased in both CCC and CCOC, with no obvious significance between them (P = 0.646). In contrast, Salvesen et al. [47] found that the loss of p63 immunostaining expression was associated with high-grade malignancy and with reduced patient survival.

The present study showed that the clear cells of CCC had cytoplasmic reactivity to p63. This is in agreement with Edwards et al. [48], who reported that p63 is expressed in some salivary gland tumors. The expression was strong in basal cell adenoma, in adenoid cystic carcinoma, and in polymorphous low-grade adenocarcinoma, and negative in canalicular adenoma. In addition, Emanuel et al. [49] found p63 positivity in adenoid cystic carcinoma so that p63-positive cells may comprise a stem cell compartment that drives the growth of this neoplasm.

In general, the myoepithelial cells present in epithelial–myoepithelial carcinoma have a characteristic clear-stained cytoplasm of polygonal cells that showed expression of p63. Therefore, the expression of p63 may be important in the diagnosis of salivary gland tumors with myoepithelial differentiation [50].

Of interest, in this present study, there was a shift in p63 expression in the majority of the cells of CCC that showed cytoplasmic staining of p63 instead of nuclear. This was in agreement with Fabbro and Henderson [51], who reported the same result. They suggested that p63 is a transcription factor involved in apoptosis, transactivation, and proliferation, and essentially stains the nucleus. They also concluded that p63 has an altered and potentially oncogenic function for the mislocalized protein in the progression and survival in prostate cancer. Furthermore, Dhillon et al. [52] concluded that higher levels of cytoplasmic p63 were significantly associated with an increased proliferative activity (Ki-67) expression and lower levels of apoptosis, which may suggest an effective oncogenic role in prostate cancer progression.

CEA shows a limited tissue expression in normal adult tissue. It is present in mucous cells and pyloric mucous cells in the stomach, columnar epithelial cells and goblet cells in the colon, in squamous epithelial cells of the tongue, cervix, and esophagus, in secretory epithelia and duct cells of sweat glands, and in epithelial cells of the prostate [53],[54].

American Joint Committee on Cancer at a recent consensus conference suggested that CEA be added to the TNM staging system for scoring colorectal cancer [55]. After successful surgical removal of colorectal cancer, an increased CEA concentration must return to the normal level within 4–6 weeks. Failure of an increased preoperative value to decrease to normal concentrations within 6 weeks after surgery is mostly associated with recurrent disease [56]. Multiple studies have shown that patients with high preoperative concentrations of CEA have worse outcome, and thus CEA has also been found to be prognostic in patients who have liver metastasis following resection for colorectal cancer [57].

In the present study, CCC showed negativity to CEA. This finding was in agreement with those obtained by Tsutsumi et al. [58] and Shi et al. [59] who showed negative staining of CEA in squamous cell carcinoma, thyroid carcinoma, hepatocellular carcinoma, nasopharyngeal carcinoma, melanoma, and different sarcomas. In contrast, CCOC showed weak positivity to CEA, with a mean of 0.87 ± 0.83, which was in agreement with Thompson et al. [60], who showed 10–50% of patients of breast carcinoma and serous ovarian carcinoma, respectively, to be positive.

In the present study, the clear cells of CCC containing glycogen showed negative cytoplasmic staining to CEA, which is in contrast to Deba et al. [61], who found that the clear cells detected in eccrine hidroadenocarcinma showed positivity to CEA. In contrast, the clear cells of trichilemmal carcinoma and also of metastatic renal cell carcinoma showed CEA negativity.

According to Kulpa et al. [62] and Nisman et al. [63], pretreatment of the CEA concentrations have an important prognostic value, but the studies by Shinkai et al. [64] and Buccheri et al. [65] do not confirm these data. In nonsmall cell lung cancer, high detectable tumor CEA expression might be an adverse prognostic factor. Patients with elevated expression of CEA may benefit from adjuvant therapy; but further series with longer follow-ups are needed for the establishment of a safe and effective management plan [66].

In addition, immunohistochemistry for markers to differentiate epithelial tumors may be helpful, and sometimes is critical, especially on small specimens. CKs are a family of water-insoluble proteins forming an essential part of the cytoskeleton of epithelial cells, and thus forms an important aid in the classification of epithelial neoplasm [67].

CK AE1/AE3 is a mixture of two different types of clones of anti-CK monoclonal antibodies, AE1 and AE3. AE1 detects the high molecular weight CKs 10, 14, 15, and 16. Clone AE3 detects the high molecular weight CKs 1, 2, 3, 4, 5, and 6, and the low molecular weight CKs 7 and 8. A broad spectrum of reactivity against both high and low molecular weight CKs is obtained. Because of the high reactivity, CK AE1/AE3 has been referred to as a 'pan-cytokeratin'. It can be used as an important 'epithelial screen' to search all epithelial differentiation [67].

Expression of pan-CK had been detected in various odontogenic lesions [68],[69] and CK19 has also been found in all kinds of odontogenic epithelial cells [70],[71]. In salivary glands and their derivative tumors, only ductal epithelial cells exhibit the focal expression of CK19 [72]. In their study, Li et al. [73] noticed that the tumor-clear cells of CCOC showed positive staining for pan-CK.

In the present study, all clear cells in CCOC and some sporadic cells in CCC showed positivity to pan-CK. These findings were in agreement with Pal and Chowdhury [74] and Patne et al. [75], who detected positivity in renal CCC of the prostate. In contrast, Singh et al. [76] and Wang and Xue [77] showed negative reactivity.

In contrast to the concept that CKs are produced in fragmented forms only by epithelial cells (due to apoptosis), Catherine et al. [78] reported a release of full-length CK19 by tumor cells, and they suggested that the release of CK19 was an essential active process and not simply a consequence of apoptosis, and that the viable tumor cells can secret CK19, which may contribute to the metastatic process among breast cancer patients. They also added that CK19 may be an indicator of aggressive behavior of disseminated breast cancer cells. Increase in the expression of CK19 may be a more accurate indicator for clinical outcome and prognostic marker in human oral squamous cell carcinoma and important molecular event in pathogenesis of oral carcinoma [79].

De Matos et al. [80] found negative CK19 staining in benign thyroid lesions, which is in contrast to Cheung et al. [81], Debdas et al. [82], and Nasr et al. [83], who showed positive expression of CK19 in goiter (20, 50, and 68%, respectively). The sensitivity and the specificity as regards CK19 in distinguishing benign from malignant were 78 and 45%, respectively. It has been suggested that CK19 may be used as a useful marker for differentiating papillary thyroid carcinoma from papillary hyperplasia [84].

Immunohistochemical studies of various antibodies to CKs have been performed to distinguish papillary from follicular thyroid tumors and to differentiate the former from non-neoplastic lesions through the differential expression of this marker in normal and neoplastic follicular cells [85]. Sunati et al. [86] found diffuse and strong staining of CK19 in almost all cases of papillary thyroid carcinoma, regardless of their subtypes. In contrast, according to the findings of Kragsterman et al. [87], CK19 is of limited value as a marker for the definite diagnosis of thyroid tumors.

Moreover, according to a study by Schmitt et al. [88], CK19 should be included in routine diagnostic methods for pancreatic neuroendocrine tumors, because it improves the prognostic value of the WHO 2004 classification. In this study, CK19 reactivity was well correlated with histopathologic factors like mitoses, vascular invasion, necrosis, solid histological pattern, and Ki-67 labeling index. In their study, Charitini et al. [89] added that CK19 might represent an important sign of stem cell capabilities of some cells and could be indicative of ductal differentiation.

In oral squamous cell carcinoma, CK19 expression has been found to correlate significantly with the grade of pathological differentiation [90]. Similarly, Chen et al. [91] observed a significant overexpression of CK19 in cutaneous squamous cell carcinoma. In contrast, Ossama et al. [92] found no significant differences in CK19 expression between actinic keratosis, carcinoma in situ, and squamous cell carcinoma.

Expression of CK has been studied in various types of odontogenic lesions [71]. In the present study, the tumor cells of CCOC showed positivity to CK19. This is in agreement with Li et al. [73], who concluded that CK19 has been shown to react with all kinds of odontogenic epithelial cells. Thus, the immunocytochemical profile of the CCOC suggests that they are of odontogenic epithelial origin.

In this study, not all cells of CCC showed CK19 positivity; only some ductal cells showed reaction to CK19. This is in line with Li et al. [73], who concluded that only ductal cells exhibit focal expression of CK19.

CD10 is a zinc-dependent metalloendoprotease that can cleave signaling peptides [93],[94]. CD10 is expressed in various normal cell types, and being an essential tissue stem cell marker of the bone marrow [95], adipose tissue [96], lungs [97], and breasts [98], CD10 is also expressed in some types of cancers, such as the kidney, liver, skin, cervix, prostate, lung, breast, pancreas, stomach, and bladder [99]. In head and neck squamous cell carcinoma, the role of CD10 in tumor growth and differentiation is important [100]; however, the underlying mechanism is not clear.

CD10 is associated with growth and differentiation of neoplastic cells, and its expression increases with an increase in tumor malignancy. In their study, Ogawa et al. [101] found that there was a negativity of CD10 in the stromal cells of normal colorectal tissue, but the presence of CD10+ stromal cells was increasing in dysplastic lesions and maximally found in the stroma adjacent to invasive carcinoma [102].

Marc et al. [103] found that patients with primary tumors expressing high levels of CD10 were more likely to have lymph node metastasis; in contrast, Osman et al. [104] proposed that loss of CD10 expression was associated with an unfavorable patient outcome. In addition, immunodetection of CD10 can be used to distinguish parotid metastasis of renal cell carcinoma from other CCC variants of the parotid gland [105].

Sayed et al. [106] concluded that Bcl-2, CD10, and CD34 are useful markers in differentiating between basal cell carcinoma and trichoepithelioma. Positive immunostaining for CD10 in stromal cells around basaloid nests favors trichoepithelioma over basal cell carcinoma. These findings may prove to be of diagnostic help in distinguishing borderline cases, and also offer some possible explanations for the biological differences between these neoplasms.

In the present study, CCC and CCOC showed 10 and 20% positive staining to CD10, respectively; this finding was in agreement with Ogawa et al. [107], who studied the expression of CD10 in colorectal carcinoma and did not find any expression of this marker, and with Saleh et al. [108], who showed negativity to both CCC and CCOT against CD10. In contrast, Fujimoto et al. [109] identified a strong expression of CD10 in patients with higher degree of metastases, which was also observed by Yao et al. [110] and Ohji et al. [111].


  Conclusion Top


CCC and CCOC are malignant, locally aggressive tumors with the capacity to metastasize. Based on current observations and immunostains, they are difficult, and in some cases impossible to distinguish morphologically and immunohistochemically despite a different cell of origin. Pan-CK, CK19, and CEA may have slightly significant difference between CCC and CCOC, but based on published data and the clinical experience, the diagnosis of these tumors mainly depends on the exclusion of other tumors. Moreover, histological and immunohistochemical analyses of neoplasm features have limited value.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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