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An Immunohistochemical Analysis of a Newly Developed, Mouse Monoclonal p40 (BC28) Antibody in Lung, Bladder, Skin, Breast, Prostate, and Head and Neck Cancers.

Products of the p63 gene may be divided into 2 major classes based on the composition of the N-terminal domain of the protein. Longer variants containing an Nterminal transactivation domain have been identified as transactivated p63, whereas shorter isoforms that lack the transactivation domain have been designated as p40 (ANp63). (1) Anti-p63 (4A4) has been shown to be a useful immunohistochemical marker for lung squamous cell carcinoma (SqCCA), and p63 has been demonstrated in breast, prostate, and head and neck cancers.2 Because antibodies for p63 (4A4) recognize both p63 and p40 proteins, p63 has proven to be a sensitive marker for lung SqCCA; however, studies have shown a lack of specificity in a subset of lung cancers, including lung adenocarcinoma (LADC). (3,4) In contrast, the p40 variant is selectively expressed in lung SqCCA, offering an opportunity for improved specificity, and p40 recognizes an epitope unique to the p40 isoform, which may result in diminished reactivity in certain lung cancer phenotypes for increased specificity.

In recent studies, a rabbit polyclonal p40 (RPp40) antibody demonstrated equivalent immunohistochemical staining versus p63 for sensitivity in lung SqCCA; however, RPp40 exhibited markedly superior specificity because it stained fewer cases of LADC and did not stain small cell lung carcinomas (3-6); however, RPp40 from different vendors, lotto-lot variation, and dilution factors could influence specificity. Determining expression levels of the trans-activated p63 and p40 isoforms has been useful in the diagnosis of cancer. In particular, p63 and RPp40 have been helpful in diagnosing cancers such as lung, bladder, breast, prostate, and head and neck cancers. (1-13) In addition, p63 has often been used in conjunction with high-molecular-weight cytokeratin (HMWCK) and a-methylacyl coenzyme A racemase (AMACR) in prostate biopsies. (14,15)

The RPp40 antibodies are commercially available. Even though RPp40 antibodies are said to have greater specificity in lung cancers, our experience with 2 commercially available RPp40 antibodies has demonstrated varying degrees of cytoplasmic background staining, and thus, they may not be suitable for use in multiplex stains, such as double stains for prostate cancer. (9) Other studies, (3) however, found no nonspecific background staining with RPp40, and thus, our findings have not been universal. Lot-to-lot variability is common with rabbit polyclonal antibodies, so mouse monoclonal antibodies may be preferable; therefore, a mouse monoclonal against p40 (MMp40; BC28) hybridoma was generated.

Our objective was to use MMp40, RPp40, and p63 in an immunohistochemical study to evaluate the sensitivity, specificity, and nonspecific background staining in lung cancers, and to test MMp40 in cancer tissues from lung, bladder, breast, skin, prostate, and head and neck.

A staining comparison was also performed between MMp40 and p63 of basal cells in prostatic intraepithelial neoplasia (PIN) and benign glands. Double-stain cocktails containing p63, HMWCK, and AMACR have routinely been used clinically for the assessment of PIN and prostatic adenocarcinomas (14,15); therefore, a triple antibody cocktail of MMp40, mouse monoclonal HMWCK, and rabbit monoclonal AMACR was evaluated with a double-stain polymer detection kit for identification of PIN and prostate adenocarcinoma.

MATERIALS AND METHODS

Formalin-fixed, paraffin-embedded tissue microarrays were constructed in-house or purchased commercially (US Biomax, Rockville, Maryland; and Pantomics, Richmond, California). Normal tissue microarrays (n = 34) were tested with MMp40 and p63 to determine specificity and sensitivity. Lung cancers (n = 40) were tested for specificity and sensitivity with antibodies MMp40, RPp40, and p63. Additional cases of lung cancer (n = 194), including LADC (n = 71; 61.4%), SqCCA (n = 67; 48.6%), large cell neuroendocrine carcinoma (n = 10; 7.2%), small cell carcinoma (n = 23; 16.7%), and mesothelioma (n = 23; 16.7%) were evaluated with MMp40 for sensitivity and specificity, and MMp40 was further evaluated in cancers of other origins (n = 212), including urothelial (n = 48; 22.6%), skin (n = 20; 9.4%), breast (n = 65; 30.7%), prostate (n = 12; 5.7%), and head and neck (n = 67; 31.6%). In an additional study, 25 simple or radical prostatectomy specimens (benign, hyperplasia, or prostatic adenocarcinoma) were stained with p63 and MMp40. Microscopically, areas of 5 benign glands and 5 PIN glands were randomly selected for counting stained cells in each prostatectomy case. Twelve cases of prostate cancer were selected based on the presence of cancer. The percentage of basal cells in the circumference of benign and PIN glands that stained positive and the nuclear staining in prostate cancers were recorded for each case.

In a feasibility study, a triple-antibody cocktail consisting of MMp40, mouse monoclonal HMWCK (34[beta]E12), and rabbit monoclonal AMACR was diluted and optimized in a modified phosphate-buffered saline diluent, followed by a cocktail of goat anti-mouse horseradish-peroxidase polymer enzyme and a goat anti-rabbit alkaline phosphatase polymer enzyme polymer. Visualization was accomplished with 3,3'-diaminobenzidine (DAB) and fast red chromogens.

Scoring Method for Interpretation

Cases with lung cancers were considered positive, if 5% or more of the tumor cells showed nuclear stain. Cases with less than 5% staining and no focal areas of positive staining were scored as negative. Cases that were mostly negative but contained small areas of tumor cells in which almost all tumor cells were positive were classified as focally positive. In other cancers types tested, cases were considered positive if at least 1% of tumor cells showed nuclear staining.

Immunohistochemistry

All tissue sections were deparaffinized in the usual manner and hydrated down to water. Slides were placed in a modified citrate buffer (Diva Decloaker, Biocare Medical, Concord, California) and heated in a pressure cooker (Decloaking Chamber, Biocare) at 110[degrees]C for 12 minutes. Antibodies p63 (4A4) (1:100), MMp40 (BC28; 1:200), and RPp40 (1:200) (Biocare) were titrated for optimum dilution using 30 minutes of incubation for all antibodies. Slides were rinsed in Tris-buffered saline wash buffer and incubated for 30 minutes in a biotin-free, goat anti-rabbit or anti-mouse horseradish peroxidase polymer detection system. Tissue sections were then visualized with DAB and briefly counterstained in a modified Mayer hematoxylin. For multiplex double stains, a triple-antibody cocktail consisting of HMW CK, p40 or p63, and AMACR was applied to tissues for 30 minutes, followed by a double-stain kit using a goat anti-mouse horseradish peroxidase, and a goat antirabbit alkaline phosphatase polymer kit (Biocare). Visualization was achieved with DAB and fast red chromogens.

Generation of the MMp40 Hybridoma

The MMp40 was developed by immunizing BALB/c mice with one or more peptides corresponding to N-terminal amino acids of the human p40 protein. The p40 peptides were conjugated with keyhole limpet hemocyanin and injected into the BALB/c mice with an adjuvant via intraperitoneal administration (5 times, at 3-week intervals). The immune reactivity of MMp40 was assessed by direct enzyme-linked immunosorbent assay on p40 peptides and recombinant p40 protein. Mice with the highest titers were chosen for developing hybridomas via cell fusion. A hybridoma clone that demonstrated the best reactivity to p40 peptides and protein was tested on human tissues. The clone was chosen and designated as BC28. The BC28 clone was further tested for isotype and identified as a mouse immunoglobulin G1. Clone BC28 antibody was produced by large-scale tissue culture of the hybridoma cells and by ascites in BALB/c mice. The BC28 demonstrated specific reactivity to human p40 protein by enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry on human tissues.

Cross-reactivity Tested by Western Blotting

The purified monoclonal antibody MMp40 (BC28) was characterized by Western blotting (Figure 1). Full-length p40 and transactivated p63-transfected cell lysates (OriGene, Rockville, Maryland) were subjected to protein gel electrophoresis using a 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Tris-glycine buffer, followed by transfer onto nitrocellulose filters in Tris-glycine buffer. Proteins on the blots were visualized by incubating p63 (4A4) and MMp40 (BC28) antibodies for 60 minutes at room temperature after use of a blocking buffer, followed by incubating with peroxidase-conjugated goat antimouse immunoglobulins. The blots were detected using 3,3',5,5'-tetramethylbenzidine membrane chromogen.

RESULTS

Nuclear staining by MMp40 was observed in the following normal tissues: basal cells in prostate; myoepithelial cells in breast; urothelial cells in bladder (but not umbrella cells); stratified squamous epithelial cells in skin, squamous mucosa in tonsil, esophagus, and uterine cervix; and cytotrophoblasts in placenta. A low staining percentage (<1%) of epithelial cells in both thymus (3 of 3; 100%) and spleen (2 of 2; 100%) was observed (Table 1); however B cells and T cells were negative. In a direct comparison of p63 versus MMp40 in normal tissue (n = 34), no differences in staining specificity were observed, except that p63 (but not MMp40) stained striated muscle (data not shown).

The MMp40 demonstrated equal staining sensitivity (34 of 40; 85%) in lung SqCCA as p63 and RPp40 did (Table 2). The MMp40 staining in lung SqCCA was clean and intense, and MMp40 was negative in 98% (49 of 50) of the cases of LADC (Figure 2, A and B). Antibodies MMp40 and RPp40 provided higher specificity (98%; 49 of 50) in LADC than p63 did (90%; 45 of 50; Table 2) because p63 stained a greater percentage of the LADC cases (P = .20). The RPp40 stained macrophages in lung tissues, whereas such staining by MMp40 was negative (Figure 3, A and B). The RPp40 antibodies also displayed cytoplasmic, nonspecific staining in neoplastic cells, whereas the MMp40 did not (Figure 3, C and D). To further assess the sensitivity and specificity of MMp40 in lung cancers, additional cases of lung SqCCA (n = 67; 48.6%) and LADC (n = 71; 51.4%) were stained. Combining results of both studies, MMp40 stained 94.4% (101 of 107) of the lung SqCCA cases and 0.8% (1 of 121) of the LADC cases (Table 3). All cases of small cell carcinoma, large cell neuroendocrine carcinoma, and mesothelioma were negative (Table 3).

In urothelial carcinoma (n = 48), MMp40 stained 85% (41 of 48) of the cases (Table 3) (Figure 4, A). In skin cancers (squamous cell and basal cell carcinomas), MMp40 stained 95% of cases (19 of 20) from various locations (Table 4; Figure 4, B). In ductal carcinoma in situ, only myoepithelial cells stained with MMp40. All infiltrating breast cancers were negative; however, in 3 cases, a few individual cancers cells were stained with MMp40 (<1%) and were thus were scored negative. All prostate cancers (12 of 12; 100%) showed negative staining with MMp40 (Table 3). In various head and neck cancers (Tables 3 and 5), MMp40 stained 81% (54 of 67) of the cases (Figure 4, C), and in both metastatic and stage IV head and neck cases combined, MMp40 stained 67% (14 of 21) of the cases (data not shown).

In benign prostate and PIN glands, almost identical staining was achieved with MMp40 and p63 (Table 6) (Figure 5, A and B). In our study, nuclear staining was not observed in any cases of prostate cancer with MMp40 or p63; however, other reports have shown occasional staining by p63 and RPp40 in prostate cancer (1.4% and 0.6%, respectively). (9) The multiplex, triple-antibody, 2-color cocktail (MMp40 [DAB], HMWCK [DAB], and AMACR [fast red]) provided excellent staining in differentiating prostate cancer from benign and PIN prostate glands (Figure 6).

COMMENT

p40 is the shortest variant of the p53 homologue for which multiple isoforms have been identified, including p40/ DNp63/AIS, p51, p63, and p73Hn Low-level amplification of the p40 gene locus, accompanied by RNA and protein overexpression, was observed in primary lung cancers and in head and neck cancer cell lines. The p40 protein overexpression in primary lung tumors was limited to squamous cell carcinoma and to tumors known to harbor a high-frequency of p53 mutations. Moreover, coexpression of p40 and p53 led to a decrease in p53 transcriptional activity; these results support the notion that p40 plays an oncogenic role in human cancer. (11)

Until recently, anti-p40 has been a relatively unknown immunohistochemical marker; however, studies have shown RPp40 to be highly specific for squamous cells, basal cells, and myoepithelial cells. (2-7,9,10) Most recently, in a study (3) of 470 cases, RPp40 staining was equivalent to p63 in lung SqCCA but demonstrated superior specificity versus p63, which helps to eliminate the consequences and potential confusion of p63+ adenocarcinomas. In our study, a cutoff value of 5% staining expression in lung cancer was adopted based on the findings of Bishop et al, (3) in which RPp40 was only focally expressed in less than 5% of the tumors cells. The study of Bishop and colleagues (3) included 205 adenocarcinomas, of which 74 (36%) were positive for p63, whereas only 7 cases (3%) showed labeling by RPp40, and in each of those cases, the extent of RPp40 reactivity was minimal, not exceeding 5% of the tumor cells. (3) In Nonaka, (4) 150 lung adenocarcinomas and 50 squamous cell carcinomas were stained with antibodies p63, TTF-1, and RPp40. Twenty-seven cases of LADC (18%) were positive for p63 to a variable extent; however, RPp40 was negative in all 150 LADC (100%). Four of 27 cases (15%) of p63+ LADC were negative for TTF-1, thus raising the real possibility that those LADC could be misidentified as SqCCAs. (4) In our study, MMp40 stained only 1 of 121 cases (0.8%) of LADC, thus confirming the high specificity of RPp40 observed in the previous studies. The MMp40 stained 101 of 107 of lung SqCCA cases (94.4%). All lung SqCCA cases in this study had been previously diagnosed as SqCCA; however, the 6 poorly differentiated lung SqCCAs (5.6%) that were negative for MMp40 were also negative for desmoglein 3, TTF-1, and napsin A, and thus, those cases could not be classified by immunohistochemistry (data not shown). In Brown et al, (6) the authors used a commercial RPp40 and achieved 92% sensitivity, thus demonstrating similar findings to our study.

In a direct comparison of basal cell staining in prostate tissues, MMp40 provided equal staining to p63; however, in certain cases, MMp40 stains were slightly cleaner and more intense than p63 (Figure 5, A and B). In a direct comparison of MMp40 and RPp40 antibodies, MMp40 provided cleaner staining because the cytoplasm in both benign glands and PIN glands showed nonspecific background staining with RPp40 (data not shown). In Sailer et al, (9) the authors concluded that the additional cytoplasmic immunoreactivity of RPp40 narrowed its eligibility for antibody cocktails (eg, with AMACR). A multiplex, double stain was developed for prostate cancer (PIN40), which included MMp40, HMWCK, and AMACR. Twenty cases of prostate cancer were compared using p63, HMWCK, and AMACR multiplex staining. The PIN40 was equivalent to the analogous cocktail containing p63 (PIN-4) (data not shown) (Figure 6).

The MMp40 antibodies stained squamous mucosa in normal cervix and normal esophagus (Table 2). Previous studies (16,17) have shown both p63 and ANp63 (RPp40) expression in esophageal, endometrial (squamous component), and cervical cancers. In our study, we stained a few sections of esophageal, endometrial, and cervical cancers that were all positive for MMp40 (data not shown); however, additional studies are needed to confirm whether MMp40 can be used with those types of cancers. We also observed staining of epithelial cells in normal spleen and thymus with MMp40. The staining of epithelial cells was also confirmed by p63 (data not shown). Epithelial cells stained with ANp63/p40 were also demonstrated in another study. (18)

Finally, 10 of 10 (100%) of the lung neuroendocrine lung cancers were negative for MMp40. In contrast, studies (19,20) have demonstrated that ANp63/p40 stains subsets of lung large cell carcinoma.

CONCLUSION

To our knowledge, this is the first report of the use of MMp40 for the differential diagnosis in non-small cell lung cancer. In this study, MMp40 (BC28) was superior to p63 in lung cancer, providing equal sensitivity in lung SqCCA, while staining a much lower percentage of LADC. The MMp40 antibody is a major advancement for its specificity in the differential diagnosis of lung SqCCA versus LADC, and MMp40 is a high-quality screening antibody for determining squamous origin of carcinoma in lung and other sites, including skin and head and neck carcinomas. The MMp40 antibody may also be an important marker for identifying urothelial carcinomas.

Please Note: Illustration(s) are not available due to copyright restrictions.

References

(1.) Nobre AR, Albergaria A, Schmitt F. p40: a p63 isoform useful for lung cancer diagnosis--a review of the physiological and pathological role of p63. Acta Cytol. 2013; 57(1):1-8.

(2.) Di Como CJ, Urist MJ, Babayan I, et al. p63 expression profiles in human normal and tumor tissues. Clin Cancer Res. 2002; 8(2):494-501.

(3.) Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N. p40 (DNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012; 25(3):405-415.

(4.) Nonaka D. A study of DNp63 expression in lung non-small cell carcinomas. Am J Surg Pathol. 2012; 36(6):895-899.

(5.) Pelosi G, Fabbri A, Bianchi F, et al. DNp63 (p40) and thyroid transcription factor-1 immunoreactivity on small biopsies or cell blocks for typing non-small cell lung cancer: a novel two-hit, sparing-material approach. J Thorac Oncol. 2012; 7(2):281-290.

(6.) Brown AF, Sirohi D, Fukuoka J, et al. Tissue-preserving antibody cocktails to differentiate primary squamous cell carcinoma, adenocarcinoma, and small cell carcinoma of lung. Arch Pathol Lab Med. 2013; 137(9):1274-1281.

(7.) Yamaguchi K, Wu L, Caballero OL, et al. Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. Int J Cancer. 2000; 86(5):684-689.

(8.) Karni-Schmidt O, Castillo-Martin M, Shen TH, et al. Distinct expression profiles of p63 variants during urothelial development and bladder cancer progression. Am J Pathol. 2011; 178(3):1350-1360.

(9.) Sailer V, Stephan C, Wernert N, et al. Comparison of p40 (DNp63) and p63 expression in prostate tissues which one is the superior diagnostic marker for basal cells. Histopathology, 2013; 63(1):50-56.

(10.) Barbareschi M, Pecciarini L, Cangi MG, et al. p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol. 2001; 25(8):1054-1060.

(11.) Hibi K, Trink B, Patturajan M, et al. AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci U S A. 2000; 97(10):5462-5467.

(12.) Choi HR, Batsakis JG, Zhan F, Sturgis E, Luna MA, El-Naggar AK. Frequent gain of the p40/p51/p63 gene locus in primary head in primary head and neck cancers. Int J Cancer. 2000; 86(5):684-689.

(13.) Saintigny P, El-Naggar AK, Papadimitrakopoulou V, et al. DNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia. Clin Cancer Res. 2009; 15(19):6284-6291.

(14.) Dabir PD, Ottosen P, Hyer S, Hamilton-Dutoit S. Comparative analysis of three- and two-antibody cocktails to AMACR and basal cell markers for the immunohistochemical diagnosis of prostate carcinoma. Diagn Pathol. 2012; 7:81. doi: 10.1186/1746-1596-7-81.

(15.) Jiang Z, Li C, Fischer A, Dresser K, Woda BA. Using an AMACR (P504S)/ 34[beta]E12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens. Am J Clin Pathol. 2005; 123(2):231-236.

(16.) Morita M, Uramoto H, Nakata S, et al. Expression of deltaNp63 in squamous cell carcinoma of the esophagus. Anticancer Res. 2005; 25(5):3533-3539.

(17.) Lin Z, Liu M, Li Z, Kim C, Lee E, Kim I. DNp63 protein expression in uterine cervical and endometrial cancers. J Cancer Res Clin Oncol. 2006; 132(12): 811-816.

(18.) Dotto J, Pelosi G, Rosai J. Expression of p63 in thymomas and normal thymus. Am J Clin Pathol. 2007; 127(3):415-420.

(19.) Rekhtman N, Tafe LJ, Chaft JE, et al. Distinct profile of driver mutations and clinical features in immunomarker-defined subsets of pulmonary large-cell carcinoma. Mod Pathol. 2013; 26(4):511-522.

(20.) Barbareschi M, Cantaloni C, Del Vescovo V. Heterogeneity of large cell carcinoma of the lung: an immunophenotypic and miRNA-based analysis. Am J Clin Pathol. 2011; 136(5):773-782.

David Tacha, PhD; Ryan Bremer, PhD; Thomas Haas, DO; Weiman Qi, PhD, MD

Accepted for publication December 5, 2013.

Published as an Early Online Release February 14, 2014.

From the Department of Research and Development, Biocare Medical, LLC, Concord, California (Drs Tacha, Bremer, and Qi); and the Department of Pathology, Mercy General Hospital, Janesville, Wisconsin (Dr Haas).

Dr Tacha is a founder, chief scientific officer, and stockholder of Biocare Medical, LLC. Drs Bremer and Qi are employees of Biocare Medical, LLC, and Dr Haas serves as a consultant and is on the Board of Advisors for Biocare Medical, LLC.

Reprints: David Tacha, PhD, Department of Research and Development, Biocare Medical, LLC, 4040 Pike Ln, Concord, CA 94520 (e-mail: dtacha@biocare.net).

Caption: Figure 1. Western blotting for mouse monoclonal p40 (BC28) and p63 (4A4).

Caption: Figure 2. a, Mouse monoclonal p40 staining in lung squamous cell carcinoma. b, Mouse monoclonal p40 negative staining in lung adenocarcinoma (original magnification X200 [a and b]).

Caption: Figure 3. a, Rabbit polyclonal p40 staining intraalveolar macrophages in lung tissue. b, Mouse monoclonal p40 was negative in intraalveolar macrophages. c, Rabbit polyclonal p40 displayed high background and specific staining in lung adenocarcinoma. d, Mouse monoclonal p40 was free of background staining (original magnification X200 [a through d]).

Caption: Figure 4. a, Mouse monoclonalp40 staining in urothelial carcinoma. b, Mouse monoclonal p40 staining in stage IVsquamous cell carcinoma of the sinus piriformes. c, Mouse monoclonal p40 staining in basal cell carcinoma of the skin (original magnifications X200 [a and b] and X100 [c]).

Caption: Figure 5. a, Mouse monoclonal p40 staining basal cells in benign prostate and prostatic intraepithelial (PIN) glands. b, p63 staining basal cells in benign prostate and PIN glands. Mouse monoclonal p40 displayed almost identical staining patterns in basal cells as that of p63 (original magnification X100 [a and b]).

Caption: Figure 6. Double-stain cocktail consisting of mouse monoclonal p40 and high-molecular-weight cytokeratin stained with 3,3'-diaminobenzidine and a-methylacyl coenzyme A racemase stained in prostate cancer with fast red (original magnification X100).
Table 1. Specificity of Mouse Monoclonal p40
Determined by Testing Normal Tissues (n = 34)

Adrenal gland, n = 3             0 (0)
Bladder, urinary, n = 3          2 (66)
Bone marrow, n = 1               0 (0)
Eye, n = 1                       0 (0)
Breast, n = 3                    3 (100)
Brain (cerebellum), n = 3        0 (0)
Brain (cerebral cortex), n = 3   0 (0)
Fallopian tube, n = 3            0 (0)
Esophagus, n = 3                 3 (100)
Stomach, n = 3                   0 (0)
Small intestine, n = 3           0 (0)
Colon, n = 3                     0 (0)
Rectum, n = 3                    0 (0)
Heart, n = 3                     0 (0)
Kidney, n = 6                    0 (0)
Liver, n = 3                     0 (0)
Lung, n = 3                      0 (0)
Ovary, n = 3                     0 (0)
Pancreas, n = 3                  0 (0)
Parathyroid, n = 3               0 (0)
Pituitary gland, n = 2           0 (0)
Placenta, n = 3                  1 (33)
Prostate, n = 3                  3 (100)
Skin, n = 3                      3 (100)
Spinal cord, n = 2               0 (0)
Spleen, n = 2                    2 (100)
Skeletal muscle, n = 3           0 (0)
Testis, n = 3                    0 (0)
Thymus, n = 3                    3 (100)
Thyroid, n = 3                   0 (0)
Tonsil, n = 3                    0 (0)
Ureter, n = 3                    3 (100)
Cervix, n = 3                    3 (100)
Uterus (endometrium), n = 3      0 (0)

Table 2. Comparison of Mouse Monoclonal p40
(MMp40; BC28), Rabbit Polyclonal p40 (RRp40),
and p63 (4A4) Antibodies in Lung Cancers (n = 90)

Lung Cancer         MMp40 (BC28),    RPp40,   p63 (4A4),
Phenotype              No. (%)      No. (%)    No. (%)

Squamous cell
carcinoma, n = 40     34 (85)       34 (85)    34 (85)

Adenocarcinoma,
n = 50                 1 (2)         1 (2)      5 (10)

Table 3. Mouse Monoclonal p40 in Various Cancers
and Phenotypes (n 1/4 493)

Cancer Type                                 Positive
                                            Specimens,
                                            No. (%)

Lung squamous cell carcinoma, n = 107       99 (92.5)
Lung adenocarcinoma, n = 121                 1 (0.8)
Lung large cell neuroendocrine, n = 10        0 (0)
Lung small cell carcinoma, n = 20             0 (0)
Mesothelioma (various phenotypes), n = 23     0 (0)
Urothelial carcinoma, n = 48                41 (85.4)
Skin cancer (squamous/basal cell), n = 20    19 (95)
Breast cancers (infiltrating), n = 65         0 (0)
Prostate adenocarcinoma, n = 12               0 (0)
Head and neck squamous cell carcinoma       54 (80.6)
  (various types), n = 67

Table 4. Mouse Monoclonal p40 and Various Skin
Tumors (n = 20)

                         Positive
                          Cases,
                         No. (%)

SqCCA Tissues            2 (100)
Parietal region, n = 2   1 (100)
Heel, n = 1              2 (100)
Cunnus, n = 2            1 (100)
Thigh, n = 1             1 (100)
L Cheek, n = 1           1 (100)
L tempus, n = 1          1 (100)
Head, n = 1              1 (100)
Face, n = 1
                         Positive
                          Cases,
                         No. (%)

BCC                      2 (100)
Tissues                  1 (100)
L eyelid                 1 (100)
Head                     0 (0)
Face                     1 (100)
Parietal region          1 (100)
Nose                     1 (100)
Ear                      1 (100)
Preauricula              1 (100)
Nasal ala
Thigh

Abbreviations: BCC, basal cell carcinoma;
L, left; SqCCA, squamous cell carcinoma.

Table 5. Mouse Monoclonal p40 and Various Head and Neck Cancers
(n = 67)

                                                            Positive
                                                            Cases,
Tissue Types                                                No. (%)

Cheek SqCCA, n = 3                                          3 (100)
Epiglottis SqCCA, n = 6                                     6 (100)
Left gingiva SqCCA, n = 1                                   1 (100)
Laryngeal pharynx SqCCA, n = 7                              6 (86)
Larynx SqCCA, n = 16                                        14 (88)
Lower lip SqCCA, n = 2                                      2 (100)
Maxillary sinus SqCCA, n = 2                                1 (50)
Nasal sinus SqCCA, n = 2                                    1 (50)
Nasopharynx SqCCA, n = 1                                    1 (100)
Nasal root SqCCA, n = 1                                     1 (100)
Mouth floor SqCCA, n = 1                                    1 (100)
Palate SqCCA, n = 2                                         2 (100)
Pharynx SqCCA, n = 1                                        1 (100)
Sinus piriformis SqCCA, n = 4                               3 (75)
Submaxilla SqCCA, n = 4                                     3 (75)
Tongue SqCCA, n = 4                                         3 (75)
Upper jaw SqCCA, n = 2                                      2 (100)
Carcinoma sarcomatoid of maxillary sinus, n = 1             0 (0)
Metastatic mucoepidermoid carcinoma of neck, n = 1          0 (0)
Metastatic mucoepidermoid carcinoma of mouth floor, n = 1   0 (0)
Metastatic SqCCA of L upper gingiva, n = 1                  0 (0)
Metastatic SqCCA of oral cavity, n = 1                      1 (100)
Metastatic SqCCA of laryngeal pharynx, n = 1                1 (100)
Metastatic acinic cell carcinoma of neck, n = 2             0 (0)

Abbreviations: L, left; SqCCA, squamous cell carcinoma.

Table 6. Prostate Gland Circumference Staininga
(n = 125)

Benign Prostate
Glands, %

MMp40  p63
68.2   67.6

Prostatic Intraepithelial
Neoplasia, %

MMp40  p63
71.1   70.2
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Author:Tacha, David; Bremer, Ryan; Haas, Thomas; Qi, Weiman
Publication:Archives of Pathology & Laboratory Medicine
Date:Oct 1, 2014
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